Clinical Trial: Lenvatinib Efficacy in Metastatic Neuroendocrine Tumors (TALENT)



Lenvatinib has just completed a Phase 2 trial in Gastrointestinal (GI) and Pancreatic Neuroendocrine Tumours.  The trial was sponsored by Grupo Espanol de Tumores Neuroendocrinos (Spanish NET scientific organisation) and the manufacturers.  A European venture with sites in Austria, Italy, Spain, UK.   Headline: The responses are better than Everolimus (Afinitor) and Sunitinib (Sutent).

What is Lenvatinib?

It is a type of targeted therapy known as a multikinase inhibitor. The brand name is ‘LENVIMA‘. These work by inhibiting multiple intracellular and cell surface kinases, some of which are implicated in tumour growth and metastatic progression of cancer, thus decreasing tumour growth and replication. A range of receptor kinases are involved in these processes, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (c-KIT), Flt3, fibroblast growth factor receptor (FGFR), which can be hyperactivated during tumour formation and progression.  Tumour growth may be prevented by inhibiting the action of these hyperactivated receptor kinases, and as tumour progression usually involves the action of multiple kinases rather than just one, it is logical to target multiple kinases.

The Lenvantinib mechanism of action is similar to targeted therapy drugs already in use (or in trial) for Neuroendocrine Tumours:

  • Sunitinib (Sutent) – a targeted therapy receptor protein-tyrosine kinase inhibitor.  It inhibits the actions of vascular endothelial growth factor (VEGF) and is an angiogenesis inhibitor (i.e. the development of blood vessels to supply the tumour with nutrients, which they need to grow).  It is a mutlikinase in inhibitor.
  • Everolimus (Afinitor) – a targeted therapy kinase inhibitor that inhibits mammalian target of rapamycin (mTor) kinase, an enzyme required for cell growth and survival. By blocking this enzyme, the medication prevents cell division and, in turn, tumor growth. The medication can also interrupt angiogenesis.
  • Cabozantinib, an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL, and currently on trial for Neuroendocrine Cancer.  Click here.

Multikinase inhibitors such as Lenvatinib, may be used to treat advanced kidney cancer as well as other specific types of cancer (in my research I also noted that in addition to kidney cancer, the drug is already approved for liver and thyroid cancers).  Worth also noting that the 3 examples of targeted therapy above are not just in use/in trial for Neuroendocrine Cancer, they are also in use/in trial for others including Renal (Kidney) Cancer, Breast Cancer.  Often more than one single kinase inhibitor can be given as a combo treatment, perhaps in sequence, to tackle multi kinases.

Anything special about Lenvatinib for Neuroendocrine Cancer? 

Recent reports from oncology conferences indicate that Lenvatinib showed significant antitumor activity and a favourable toxicity profile in progressive advanced NETs. This is the highest reported ORR with a targeted agent, confirmed by central radiology assessment in pancreatic NETs and Gastrointestinal (GI) NETs with promising progression free survival (PFS) in a pre-treated population; further evaluation is warranted.

Adverse events were mild to moderate in 90% of patients, the most frequent being fatigue, diarrhea and hypertension.

Lenvatinib showed the highest reported overall response rate (ORR) by central radiology assessment with a targeted agent in advanced NETs:

Average 29.2%

pNETs: 40.4% (95% CI 27.3-54.9),

GI NETs: 18.5% (95% CI 9.7-31.9.

Worth noting that Everolimus and Sunitinib were approved with ORRs much less than these figures.

What’s next? 

Given the responses in comparison to other approved targeted agents, a phase 3 trial should be anticipated.  Studies are “currently ongoing” and “further evaluation warranted”.  I will keep this article live to provide updates.

New Trial using Lenvatinib and Everolimus in Treating Patients With Advanced, Unresectable Neuroendocrine Tumors

Under ClinicalTrials.gov Identifier: NCT03950609, there is a trial being setup at MD Anderson in Texas USA.  Use of a combo of Lenvatinib along with Everolimus (Afinitor) in treating patients with advanced, unresectable Neuroendocrine Tumors (the word ‘Carcinoid’ is used in the trial documentation).

Reference material used in the compilation of this article:

1. Annals of Oncology – Efficacy of Lenvatinib in patients with advanced pancreatic (panNETs) and gastrointestinal (giNETs) grade 1/2 (G1/G2) neuroendocrine tumors: Results of the international phase II TALENT trial (GETNE 1509) 23 Oct 2018 –  click here.

2. ESMO Congress 2018 – Efficacy of Lenvatinib in patients with advanced pancreatic (panNETs) and gastrointestinal (giNETs) grade 1/2 (G1/G2) neuroendocrine tumors – click here

3. Prime Oncology Slide Show – click here (useful)

4. Clinical Trials Document NCT02678780 – click here

5. Manufactures website – click here.

6.  Clinical Trials Document NCT03950609 for the trial of combo treatment Lenvatinib and Everolimus.  Click here.   As at 15 May 2019, the trial was not recruiting but see document for contact details, quite often these documents can be behind in updating. Trial start date recorded as 30 June 2019.

Thanks for reading

Ronny

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Diabetes – The NET Effect


My chest infection is now settled, as too is the excitement and apprehension behind my first ever Ga68 PET – the outcome of that is still a work in progress. Earlier this year, my thyroid ‘lesion’ on watch and wait was given a ‘damping down’ with the prescription of a thyroid hormone supplement but I await a re-ignition of that small bush fire downstream.

Bubbling behind the scenes and clamoring for attention is the spiking of my blood glucose test results and I was very recently declared ‘at risk’ for diabetes One of my followers entitled a post in my group with “The hits keep coming” in reference to encountering yet another problem in the journey with Neuroendocrine Cancer. I now know how she feels, this issue is a bit of a ‘left fielder’. However, having analysed the situation and spoken to several doctors, I can now put pen to paper.

Neuroendocrine Cancer is not a household name (…… I’m working on that) but diabetes certainly is. The World Health Organisation reports that the number of adults living with diabetes has almost quadrupled since 1980 to 422 million adults. In USA, estimates from CDC stated around 10 million people diagnosed with diabetes with a further 84 million in pre-diabetes state (at risk). In UK around 3.7 million people have diabetes with about 4 times that amount ‘at risk’. It’s a growth industry (…….. but so is NETs – in the last 40 years, the incidence of NETs is rising at a faster rate than diabetes, a disease which some writers have described as an epidemic).

With those numbers, it follows that many NET patients will be diabetic before diagnosis, some will succumb to diabetes whether they have NETs or not, and some may have an increased risk of succumbing due to their treatment. Some may even be pushed into diabetes as a direct result of their NET type or treatment. It’s important to understand diabetes in order to understand why certain types of NET and certain treatments could have an involvement.

The Pancreas

For understanding of this article, it’s worth noting the pancreas has two main functions: an exocrine function that helps in digestion and an endocrine function that regulates blood sugar. I have talked about the exocrine function in relationship to Neuroendocrine Cancer at length – check out this article on Pancreatic Enzyme Replacement Therapy. In this article, I now want to cover the issues with the endocrine function and blood sugar. First a short primer on diabetes – it is necessarily brief for the purposes of this article.

 

Diabetes Primer

TypeS OF DIABETES

Type 1 and Type 2 Diabetes are fairly well-known. There’s actually more than two types, but these are the most common. Type 2 is the most prevalent with around 90% of diabetes cases. When you’ve got Type 1 diabetes, you can’t make any insulin at all. If you’ve got Type 2 diabetes, the insulin you make either can’t work effectively, or you can’t produce enough of it. Additional types may come up in the subsequent discussion.

What is the problem?

What all types of diabetes have in common is that they cause people to have too much glucose (sugar) in their blood. But we all need some glucose. It’s what gives us our energy. We get glucose when our bodies break down the carbohydrates that we eat or drink. And that glucose is released into our blood. We also need a hormone called insulin. It’s made by our pancreas, and it’s insulin that allows the glucose in our blood to enter our cells and fuel our bodies.

If you don’t have diabetes, your pancreas senses when glucose has entered your bloodstream and releases the right amount of insulin, so the glucose can get into your cells. But if you have diabetes, this system doesn’t work properly. Diabetes is associated by being overweight but there isn’t a 100% correlation with that. However, when an individual becomes overweight, there is an increase in free fatty acids in the blood stream which may contribute to reduced insulin sensitivity in the tissues, leading to increased glucose levels in blood.

Symptoms and diagnosis of Diabetes

Different people develop different symptoms. In diabetes, because glucose can’t get into your cells, it begins to build up in your blood. And too much glucose in your blood causes a lot of different problems. To begin with it leads to diabetes symptoms, like having to wee a lot (particularly at night), being incredibly thirsty, and feeling very tired. You may also lose weight, get infections like thrush or suffer from blurred vision and slow healing wounds.

I see these symptoms mentioned very frequently and normally people are trying to associate them with NETs and/or the treatment for NETs.

Diabetes diagnosis is normally triggered diagnosed based on blood tests such as fasting Blood Glucose (snapshot) and/or Glycated Hemoglobin (A1C) or HbA1C.

Complications

Over a long period of time, high glucose levels in your blood can seriously damage your heart, your eyes, your feet and your kidneys. These are known as the complications of diabetes.

But with the right treatment and care, people can live a healthy life. And there’s much less risk that someone will experience these complications.

What are the direct connections with Diabetes and NETs?

It’s not surprising that diabetes is mostly associated with Neuroendocrine Tumors of the Pancreas but there are other areas of risk for other types of NETs including to those who are existing diabetics – see below.

Surgery

The main types of surgery for Neuroendocrine Tumors of the Pancreas are Distal Pancreatectomy (tail), Sub-total pancreatectomy (central/tail), Classic Whipple (pancreaticoduodenectomy – head and/or neck of pancreas), Total pancreatectomy (remove the entire pancreas) or an Enucleation (scooping out the tumour with having to remove too much surrounding tissue). From the PERT article link above (exocrine function), you can see why some people need this treatment to offset issues of reduced production of pancreatic enzymes. The same issue can develop with a reduced endocrine function leading to the development of diabetes.

NET Syndromes

The different types of functional pancreatic NETs often called syndromes in their own right due to their secretory role. One might think that Insulinomas are connected to diabetes issues but this hormonal syndrome is actually associated with low blood sugar (hypoglycemia), although low blood sugar can turn out to be a complication of diabetes treatment.

A NET syndrome known as Glucagonoma (a type of functional pancreatic NET) is associated with high blood glucose levels. About 5-10% of pancreatic neuroendocrine tumors are Glucagonomas, tumors that produce an inappropriate abundance of the hormone glucagon. Glucagon balances the effects of insulin by regulating the amount of sugar in your blood. If you have too much glucagon, your cells don’t store sugar and instead sugar stays in your bloodstream. Glucagonoma therefore leads to diabetes-like symptoms (amongst other symptoms). In fact Glucagonoma is sometimes called the 4D syndrome – consists of diabetes, dermatitis, deep venous thrombosis (DVT), and depression.

Another functional pancreatic NET known as Somatostatinoma is prone to developing insulin resistance. Somatostatinomas produce excessive amounts of somatostatin which interferes with the insulin/glucagon function and could therefore lead to diabetes.

Diabetes caused by cancer or cancer treatment

Worth noting that this type of diabetes is sometimes known as ‘Pancreatogenic diabetes’ and this is actually classified by the American Diabetes Association and by the World Health Organization as type 3c diabetes mellitus (T3cDM) and refers to diabetes due to impairment in pancreatic endocrine function due to acute cancer and cancer treatment (and several other conditions). The texts tend to point to cancers (and other conditions) of the pancreas rather than system wide. Prevalence data on T3cDM are scarce because of insufficient research in this area and challenges with accurate diabetes classification in clinical practice. (Authors note: Slightly confusing as many text say that type 3 diabetes is proposed for insulin resistance in the brain (diabetes associated with Alzheimer’s disease).  There’s another term for a complete removal of the entire pancreas – Pancreoprivic Diabetes

Other treatment risks

Somatostatin Analogues (e.g. Octreotide and Lanreotide) are common drugs used to control NET Syndromes and are also said to have an anti-tumor effect. They are known to inhibit several hormones including glucagon and insulin and consequently may interfere with blood glucose levels. The leaflets for both drugs clearly state this side effect with a warning that diabetics who have been prescribed the drug, should inform their doctors so that dosages can be adjusted if necessary. The side effects lists also indicates high and low blood glucose symptoms indicating it can cause both low and high blood glucose (hypoglycemia and hyperglycemia). For those who are pre-diabetic or close to pre-diabetic status, there is a possibility that the drug may push blood tests into diabetic ranges.
Afinitor (Everolimus). The patient information for Afinitor (Everolimus) clearly states Increased blood sugar and fat (cholesterol and triglycerides) levels in blood: Your health care provider should do blood tests to check your fasting blood sugar, cholesterol and triglyceride levels in the blood before you start treatment with AFINITOR and during treatment with AFINITOR”
Sutent (Sunitinib). The patient information for Sutent (Sinitinib) clearly states that low blood sugar (hypoglycemia) is a potential side effect. It also advises that low blood sugar with SUTENT may be worse in patients who have diabetes and take anti-diabetic medicines. Your healthcare provider should check your blood sugar levels regularly during treatment with SUTENT and may need to adjust the dose of your anti-diabetic medicines.

In rare cases, certain NETs may produce too much Adrenocorticotropic hormone (ACTH), a substance that causes the adrenal glands to make too much cortisol and other hormones. This is often associated with Cushing’s syndrome. Cortisol increases our blood pressure and blood glucose levels with can lead to diabetes as a result of untreated Cushing’s syndrome.

Summary

I think it’s sensible for all NET patients, particularly those with involvement as per above and who are showing the signs of hypoglycemia and hyperglycemia, to be checked regularly for blood glucose and if necessary HbA1c. Many patient information leaflets for the common NET treatments also indicate this is necessary. Always tell your prescribing doctors if you are a diabetic or about any history of low or high blood glucose before treatment for NETs.

My brush with Diabetes (as at Jan 2019)

My blood glucose levels started to climb slightly in 2016 but HbA1c remained normal. However, an HbA1c test in early 2018 put me into pre-diabetic range (44 mmoL/moL). I explained some of the above article to my GP who is corresponding with a diabetes expert at secondary care – the expert suggested that I need to be monitored carefully as weight loss is not necessarily the best response. I have kept my NET team up to date.

At the time of updating, two separate and sequential HbA1c tests (3 month interval) came back normal at 36 mmoL/moL.  I’m pragmatic enough to know that I do not need to lose weight as one of the aims of reducing my blood glucose and HbA1c levels (something emphasised by the above mentioned diabetes specialist).

I even got on my bike to do a little bit more exercise just in case!

At this point, I cannot yet say if this is the beginning of progressive Type II diabetes or if my medication is causing these spikes in my blood glucose and HbA1c. Judging by 2 x normal HbA1c, looks like the somatostatin analogue (Lanreotide in my case) may caused a spike to a pre-diabetes score.  I will keep you posted.

Summary – if you are noticing these symptoms, get your blood sugar checked (with acknowledgement to Dr Pantalone from Cleveland Clinic)

1. You’re making more trips to the bathroom

Having to go to the bathroom more than normal, particularly at night, is a sign that your blood sugar might be out of whack.

Dr. Pantalone says one of his patients came in for a diagnosis after a family member noticed that he was using the bathroom during each commercial break when they watched TV.

2. You’re getting frequent urinary or yeast infections

When your blood sugar is high and your kidneys can’t filter it well enough, sugar ends up in the urine. More sugar in a warm, moist environment can cause urinary tract and yeast infections, especially in women.

3. You’re losing weight without trying

If you have diabetes, your body isn’t able to use glucose (sugar) as effectively for its energy. Instead, your body will start burning fat stores, and you may experience unexpected weight loss.

4. Your vision is getting worse

High sugar levels can distort the lenses in your eyes, worsening your vision. Changes in your eyeglass prescription or vision are sometimes a sign of diabetes.

5. You’re feeling fatigued or exhausted

Several underlying causes of fatigue may relate to diabetes/high sugar levels, including dehydration (from frequent urination, which can disrupt sleep) and kidney damage.

This feeling of exhaustion is often persistent and can interfere with your daily activities, says Dr Pantalone.

6. You’re noticing skin discoloration

Something that Dr. Pantalone often sees in patients before a diabetes diagnosis is dark skin in the neck folds and over the knuckles. Insulin resistance can cause this condition, known as acanthosis nigricans.

 

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

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Sapanisertib – a drug on trial for Neuroendocrine Tumors (NET) with a pancreatic primary


Researchers are testing the drug Sapanisertib to see if it can halt the progression of pancreatic NETs (pNETs) which cannot be surgically removed, have not responded to other treatment, and have spread to other parts of the body.

What is Sapanisertib?

Sapanisertib is one of a group of targeted therapy drugs that interferes with tumor progression by inhibiting an enzyme known as mTOR which a tumor cell needs for growth.  In fact this is the same technique used in Afinitor (Everolimus), already approved for NETs.

It is also being tested in a number of different advanced cancers, including bladder, kidney, breast, liver, and certain types of lung cancers, among others.

The Clinical Trial

The primary goal of the phase II study is to evaluate how well pNET tumors respond to Sapanisertib. To qualify for this trial patients must have advanced pNET that cannot be surgically removed, and which have not responded to previous treatment with similar drugs. All participants will receive Sapanisertib, and will be checked periodically to see if their tumors are responding to the drug.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided at this link which provides more details about the Sapanisertib pNET trial – click here and check the inclusion and exclusion criteria; and other data.  There are 354 study locations across the USA.

Please also note this drug development was part funded by the NET Research Fundation – read more here.

Thanks for reading

Ronny

I’m also active on Facebook.  Like my page for even more news.  I’m also building up this site here: Ronny Allan

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Update: Management of Neuroendocrine Tumors

This is an excellent and positive video based overview of where we are with the Management of NETs.  This is a presentation from a NET Specialist (who some of you may know) presenting to a “GI Malignancies” conference.  This is therefore not only awareness of NETs, it’s also some good education for non NET GI experts who may only know the very basics. Useful for patients too!  I met Dr Strosberg in Barcelona (ENETS 2017) and thanked him for his presentational and scientific paper output which I often use in my articles.

The classification picture is good as it explains the different facets of NETs and how NETs are classified and categorised in a general way – not seen it done this way before.   Slightly out of date as it does not adequately convey the possibility of a well differentiated high grade recently classified by the World Health Organisation – read more here.

Amazingly it is delivered without using the word ‘carcinoid’ other than in reference to syndrome, indicating it can be done and is something also being reflected in all my posts to ensure they are up to date with the latest nomenclature.  It’s also a good example for GI doctors as this branch of medicine is often involved in NET diagnostics and surveillance.

Excellent update of all the trials which have introduced treatments in the last decade.

Screenshot 2017-12-12 16.34.54

Great update and worth the 30 minutes it takes to watch – you can view it CLICK HERE.

 

 

All graphics courtesy of www.oncologytube.com

Thanks for reading

Ronny

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Expanding PRRT – Trial of 177Lu-Edotreotide (Solucin®) – COMPETE Phase 3 Clinical Trial

ITM_header_products_endolucinbeta
graphic courtesy of ITM AG

In the News.

On the heels of the approval of PRRT in USA and whilst we all wait on positive national announcements of PRRT approval in UK and elsewhere, here’s news of a new PRRT compound undergoing a phase 3 clinical trial.  Isotopen Technologien München AG (ITM), a specialized radiopharmaceutical company, today announced the enrolment of the first patient recruited in Europe for the COMPETE phase III clinical trial at the University Hospital Marburg, Germany. The CEO of ITM said “This marks the starting point of COMPETE in Europe, whereby we expect a rapid increase in the number of recruits.”  I actually met these guys at ENETS 2018 – sounds great.

What is the COMPETE trial?

COMPETE is led as an international pivotal multi-center phase III clinical trial evaluating the efficacy and safety of (no-carrier-added) n.c.a.177Lu-Edotreotide (Solucin®) and the trial is comparing it to Everolimus (Afinitor). The trial runs until Dec 2020. The enrolment requires patients with inoperable, progressive, somatostatin-receptor positive neuroendocrine tumors of gastroenteric or pancreatic origin (GEP-NET). The primary endpoint is progression-free survival (PFS). The study will be conducted predominantly in Europe, North America, South Africa and Australia. The first patient to be enrolled and treated was in Australia.  The clinical trial document (see references below) indicates its for non-functional GI tumours but for non-functional and functional pNETs. The list of locations can also be found in the clinical trial document. The usual inclusion/exclusion rules apply but the most notable would appear to be an exclusion for those with prior exposure to any PRRT or mTor inhibitor such as Everolimus (Afinitor).

What is 177Lu-Edotreotide (Solucin®) ?

The compound under investigation, Solucin®, is known as a Targeted Radionuclide Therapy (TRT) agent, which consists of the targeting molecule Edotreotide, an octreotide-derived somatostatin analogue and ITM´s EndolucinBeta® (no-carrier-added Lutetium-177). EndolucinBeta® is a synthetic, low-energy beta-emitting isotope of Lutetium, a recently EMA approved pharmaceutical precursor. The radiopharmaceutical Solucin® is administered as an intravenous infusion, specifically targeting and destroying the tumor cells with ionizing radiation. Solucin® received an Orphan Designation (EMA/OD/196/13) for the treatment of GEP-NET, based on early clinical experience, which has demonstrated a substantial clinical benefit with increased PFS and quality of life.

From ITM’s website … “Edotreotide contains DOTA which functions as a chelator for radioisotopes and TOC, a synthetic Somatostatin receptor ligand” (chelator and ligand are just fancy names for ‘bonding’ or ‘binding’). “The compound Edotreotide binds with high affinity Somatostatin receptors and retains both its receptor binding properties and its physiological function when labeled with 177Lu. Somatostatin receptors are predominantly overexpressed by neuroendocrine tumors. 177Lu-Edotreotide, upon binding to Somastotatin receptors in vivo is internalized and retained by tumor cells.” 

“Compared to 90Y-Edotreotide, 177Lu-Edotreotide Targeted Radionuclide Therapy in NET was found to be less haematotoxic and associated with a longer median overall survival. That was highly significant for patients with low tumor uptake as well as for patients with extra hepatic and solitary metastases. In a retrospective Phase II trial 177Lu-Edotreotide showed a low uptake/dose delivered to normal organs and very high tumor-to-kidney ratio.”

Other Spin offs from ITM

Interestingly the company is also working on a ‘theranostic pair’ for imaging and treating bone metastases – see graphic below.  It does not say whether this includes NET bone metastases but I don’t see why not given the connection with Solucin. However, please note this is some years away from fruition.

graphic courtesy of ITM AG

 

References:

1.  ITM News Release – click here

2. ITM Website – click here

3. Clinical Trials Document – click here

4. FDA authorises trial to go ahead in USA – click here

5. Useful video about the trial – click here

 

Thanks for listening

Ronny

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Lanreotide for Lung NETs – SPINET Clinical Trial

Somatuline (Lanreotide)

There’s been a lot of action in the area of what is termed Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP-NETs).  It can therefore sometimes appear that Lung NETs are the poor relation.  There are certainly some unmet needs in this area of the anatomy including a lack of research.  Thus far, no prospective trials specifically for patients with lung NETs appear to have been reported.

However, there has been some recent movement. Last year, the use of Afinitor (Everolimus) was approved for progressive, non-functional NET of GI or Lung origin.

SPINET Trial for Lung NETs

In late 2016, I tipped you off about an Ipsen sponsored trial for Lung NETs involving Lanreotide (Somatuline) SPINET is a Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of Lanreotide plus “Best Supportive Care” (BSC) versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical lung NETs.   The aim of the SPINET study is to evaluate the safety and antitumor efficacy of Lanreotide 120 mg in patients with advanced lung NETs.  I suspect that many Lung NET patients are already receiving somatostatin analogues (Octreotide/Lanreotide) but prescribed only for syndrome/symptom control.

SPINET is now recruiting in many locations (see below).

The countries involved in the SPINET trial are as follows (in case my post goes out of date – see the latest update to the trials document here). Please also check the inclusion and exclusion criteria.

USA, Austria, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, UK.

In addition to the trial document linked above, you can read more about the SPINET trial here with commentary from a well-known NET Specialist – Dr Diane Reidy-Lagunes, who is the principal investigator for the trial.

How do I get on the trial?

You may be interested in this organisation – Trialbee.  They are a company helping Ipsen to raise awareness of the SPINET trial using a cloud based platform to connect patients, investigators and sponsors (I’ve authenticated their participation with Ipsen).  There is no fee for using their services.  There’s a useful questionnaire which can help you decide if this trial is for you – here.

Please note, if you are concerned about participating in clinical trials, you should always consult your specialist for advice.  

If you are a patient advocate or an advocate organisation, please share with your communities in order that Lung NET patients are at least made aware of the trial.

 

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NETwork with Ronny © – Community Newsletter JUNE 2017

 

Hi NETworkers!

Welcome to my monthly ‘Community’ newsletter. This is June 2017’s monthly summary of Ronny Allan’s Community news, views and ICYMI (in case you missed it!).

NET News

The following news items may be of interest:

  • NETs in the UK National News.  Great publicity.  Featuring NET Patient Foundation.  Click here.
  • Personalised PRRT is highlighted.  Click here.
  • Everolimus and Sunitinib. In England, NICE approves Everolimus (Afinitor) and Sunitinib (Sutent). Read more by clicking here.
  • Videos from LACNETS.  I’ve not watched them all yet due to holiday but they are always great!  Click here.
  • PRRT.  News of a PRRT trial being set up for Inoperable Pheochromocytoma/ Paraganglioma. Not yet recruiting but read more here.
  • Immunotherapy.  Merkel Cell Carcinoma is already benefiting from an FDA approved drug with another pending.  Check out this link.
  • Awareness.  Giovanni from LACNETS generates awareness in her local area – I have no doubt that awareness saves lives.  Read here.
  • Lanreotide.  Ipsen announces approval in Japan for treating NETs.   Click here.

NET Cancer Blog Activity

June was a slower month in ‘new’ blogging terms mainly due to holiday but even during this holiday, I’m being invited to external projects and a continuing flow of private messages. I’m still suffering with back pain but patiently waiting to see a physiotherapist. However, despite a low month for brand new blogs, I still managed for the first time to break through the monthly blog view figure of 20000.  ……..Thank you all so much, a lot of this was down to your support for some scheduled posts whilst I was on holiday ♥

I continue to receive a steady flow of private contacts, mainly from patients seeking information.  I don’t have an issue with private contact but please note my disclaimer.  Please also note that I cannot accept telephone calls on a one to one basis.  The number of non-patients contacting me for other reasons (mainly to help with something) continues to grow and this is producing some great publicity and awareness.

I’ve been nominated for the 2017 WEGO Health Awards in three categories so far, Blog, Patient Leader Hero and Lifetime Achievement.  If you remember last year, I made it to the final in two categories of Blog and Community and won the latter.   The nominations period ends on 7th July and I’ll let you know how you can vote for me. A vote for me is a vote for Neuroendocrine Cancer awareness.

BREAKING NEWS (…ish).  I’ve been accepted as a ‘Cure Today’ contributor which means my articles will get a wider distribution than they do now.  I’ve not contributed yet but clearly they will be posted on all my social media outlets for you to read.   You can see my profile here: http://www.curetoday.com/community/contributors

 

New (or significantly updated) Blogs Published

Due to the vagaries of Facebook inner workings, some of these may not have even shown on your Facebook timeline.  So, ICYMI …….here’s a summary with links:

Awareness Activity in June 2017

New Audiences for NET Cancer.  From Day 1, I said it was my aim to find new audiences for NETS rather than just share stuff within our own community.

  • I’m ‘extremely’ active on twitter and I find a lot of my research stuff there. I also use it to support other conditions and it’s mostly returned (i.e. others help with NET awareness and are made aware of NETs in the process). There is so much on twitter that I could swamp the community Facebook site so I started a twitter newsletter via an app called Nuzzel which seeks out stuff I normally like. Click this link and sign up if you think this is something you’d be interested in receiving.  Currently 239 subscribers – up 25% on last month.
  • I continue to be featured by ‘external’ organisations such as WEGO and my PODCAST is reaching new audiences – click here.  Other irons are in the fire but unable to bring you firm news just yet.
  • I’m proud to be a ‘Community Champion’ on the Macmillan Cancer Support Forum helping outliers from the NET community there. I’ll be reporting more on this in the coming weeks.  This is the biggest cancer support organisation in the UK.
  • I’ve been accepted as a ‘Cure Today’ contributor which means my articles will get a wider distribution than they do now.  I’ve not contributed yet but clearly they will be posted on all my social media outlets for you to read.  Click here to read more.

Speaking Engagements

  • On 7 July, I’ve been invited to speak for 10 minutes at the PLANETS patient conference in Southampton.  This is special for me as it’s where my major treatments took place and some of my medical team will be there.
  • On 5th October, I’ve been invited to speak for around an hour at the Cardiff (South Wales) NET Patient meeting (moved from July due to forecast low attendance)  Things are starting to happen in this area and I already know Dr Mo Khan who is a NET specialist working hard on behalf of patients.  I’m really looking forward to visiting and talking to this group.

Writing and other types of Engagement (external)

On 12 July, I’ve been invited to speak to Ipsen (UK). Still setting up this short notice meeting, details to follow in a separate post.  Additionally, I was interviewed by a health reporter and separately by a health consultant. I’m not at liberty to provide details yet but if anything is published in the public domain, I will of course publish it on my social media channels.

Remember …….

Social Media and Stats

Blog Milestone.  In June, I tipped over 310000 views! Thank you all so much Keep sharing! On track for 400000 by end of the year.

Facebook Milestone.  I’m aiming for 5000 followers by year-end and this is on track. The Facebook page is now my biggest outlet for awareness and education so please please please recommend this page to anyone you think would be interested.

Instagram

I’m expanding into Instagram to see how that goes. I’ve amassed over 200 followers to date. Initially, I’ll just be posting pictures of things that inspire me, mostly scenic photos of places I’ve been or want to go!  You can follow me here:  Click here to go to my Instagram page

Figures

Where did June 2017 Blog views come from? – Top 10 countries:  Germany on the up (wunderbar). And thanks to USA!

 

For interest. the 10 Ten Facebook followers by Country – Germany still sneaking up (wunderbar wieder).  Interestingly Canada always reads more than Australia despite fewer followers.

 

WOW!  – that’s an amazing amount of awareness and hopefully, support for others.  However, I cannot do this without you guys liking, commenting and sharing!  The likes give me motivation, the comments (and private messages) give me inspiration (or at least a chance to explain further) and the sharing gives me a bigger platform.  A bigger platform generates more awareness.

Thanks for your great support in June.  Onwards and upwards!

Thanks for reading

Ronny

Hey, I’m also active on Facebook.  Like my page for even more news.

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Check out my Podcast (click and press play)

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

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NETwork with Ronny © – Community Newsletter MAY 2017

Hi NETworkers!

Welcome to my monthly ‘Community’ newsletter. This is April 2017’s monthly summary of Ronny Allan’s Community news, views and ICYMI (in case you missed it!).

This year, it’s occurred to me that I’ve gone beyond just being known as a ‘blog’ and have transformed into something with a much wider focus within the NET Community and beyond. I’ve added a new section called NET News. This is a catch up of stuff I’ve accumulated over the past month but perhaps not yet posted or simply want to emphasise what I think is significant news about NETs or might impact or influence NETs  This section replaces ‘Highlights’ which will be renamed to ‘NET Cancer Blog Activity’ and cover my efforts to generate awareness and to help others.

NET News

The following news items may be of interest:

  • PRRT.  Advanced Accelerator Applications (AAA) the manufacturers of Lutathera for PRRT have announced they are on track for a mid year resubmission of the data (NDA) to the US FDA for their consideration and hopefully approval.  They also indicated that the EMA authorisation may happen in Q3 (period 1 July – 30 September) – this would be key for UK where the treatment was withdrawn from routine service in 2015.  Read more here.
  • New Trial.  Based on use of an immunotherapy drug ATEZOLIZUMAB (Tecentriq) combo’d with BEVACIZUMAB (more well known as Avastin) which is a type of biological therapy.  Click here.
  • Everolimus and Sunitinib. In England, NICE approves Everolimus (Afinitor) and Sunitinib (Sutent). Read more by clicking here.

NET Cancer Blog Activity

Like April, May was a slower month in ‘new’ blogging terms due to a number of external projects and a continuing flow of private messages. I continue to suffer back pain but my GP is now sending me to a physiotherapist (I sometimes forget I’m a patient too!). However, despite a low month for brand new blogs, I still managed to accumulate the third biggest monthly blog views ever.  ……..Thank you all so much ♥

I continue to receive a steady flow of private contacts, mainly from patients seeking information. I don’t have an issue with private contact but please note my disclaimer.  The number of non-patients contacting me for other reasons (mainly to help with something) continues to grow.

BREAKING NEWS:  I’ve been nominated for the 2017 WEGO Health Awards in two categories so far, Blog and Patient Leader Hero.  If you remember last year, I made it to the final in two categories of Blog and Community and won the latter.   I’ll bring you more details in due course.

Speaking Engagements

On 7 July, I’ve been invited to speak for 10 minutes at the PLANETS patient conference in Southampton.  This is special for me as it’s where my major treatments took place and some of my medical team will be there.

On 13 July, I’ve been invited to speak for around an hour at the Cardiff (South Wales) NET Patient meeting.  Things are starting to happen in this area and I already know Dr Mo Khan who is a NET specialist working hard on behalf of patients.  I’m really looking forward to visiting and talking to this group.

Writing and other Engagements (external)

I contributed to an article written by the CEO of WEGO Health about the spread of fake health news (miracle cures etc).  You can read the post here –On Facebook fake news can be life or death

I wrote an article for Macmillan Cancer Support which is due to be published on 5 Jun 2017 (will post next week).  This is part of Macmillan Volunteers week and I volunteered to write about my recent experience in becoming a Macmillan Community Champion.

I took part in a Macmillan poster campaign last year and finally got to stand next to a working poster in my home town of Dundee!  Here’s me here next to the poster:

There are one or two others but they are not firm yet – but you’ll be the first to know when I know!

New (or significantly updated) Blogs Published

Due to the vagaries of Facebook inner workings, some of these may not have even shown on your Facebook timeline.  So, ICYMI …….here’s a summary with links:

Awareness Activity in May 2017

New Audiences for NET Cancer.  From Day 1, I said it was my aim to find new audiences for NETS rather than just share stuff within our own community.

  • I’m ‘extremely’ active on twitter and I find a lot of my research stuff there. I also use it to support other conditions and it’s mostly returned (i.e. others help with NET awareness). There is so much on twitter that I could swamp the community Facebook site so I started a twitter newsletter via an app called Nuzzel which seeks out stuff I normally like. Click this link and sign up if you think this is something you’d be interested in receiving.  Currently 192 subscribers – up 20% on last month.
  • I continue to be featured by ‘external’ organisations such as WEGO and my PODCAST is reaching new audiences – click here.  Other irons are in the fire but unable to bring you firm news just yet.
  • I’m making new friends in the interventional radiologist community and am waiting on a video featuring a NET Patient (will bring you details in due course) and I’m learning more about these technologies from reading their tweets – I had no idea how many different jobs these guys do! I’m also seeing an increase from the Pathology community.  The trailer for the documentary which will feature a NET Patient can be found by clicking here.  The actual documentary is now available on Vimeo and Amazon Prime.
  • I’m proud to have been asked to become a ‘Community Champion’ on the Macmillan Cancer Support Forum helping outliers from the NET community there. I’ll be reporting more on this in the coming weeks.

Patients Included.  A new campaign for 2017. I was excited to have been invited to the first ever joint Patient-Physician symposium at the annual ENETS conference in Barcelona 8 – 11 March. I have really good information which will feed into my blogs, either as updates or new blogs. This new blog is a result of attending this symposium but it’s from an existing campaign run along the ‘Consequences’ campaign run by Macmillan Cancer Support for all cancers. In the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life

the first question to the first ever joint patient-physician symposium. Hardly any voice due to a winter cold

Social Media and Stats

Blog Milestone.  In May, I tipped over 290,000 views! Thank you all so much Keep sharing!

Facebook Milestone.  I’m aiming for 5000 followers by year-end and this is on track. The Facebook page is now my biggest outlet for awareness and education so please please please recommend this page to anyone you think would be interested.

Instagram

I’m expanding into Instagram to see how that goes. I’ve amassed over 200 followers to date. Initially, I’ll just be posting pictures of things that inspire me, mostly scenic photos of places I’ve been or want to go!  You can follow me here:  Click here to go to my Instagram page

Figures

  • Facebook 4689.  This is a key outlet for my blog – please encourage others to like my page (if you’d like to know how to use your Facebook to invite others to my page – let me know, I can provide you with a step by step approach). Please also join my 2017 awareness campaign event here (select ‘Going’)
  • Twitter3915 / 3017 Follow me here @RonnyAllan1 / @NETCancerBlog
  • Total Blog Views: 292,626
  • Blog with most views: 9211The Anatomy of Neuroendocrine Cancer 
  • Most blog views in one day:  2043 on 15 Jan 2017.  Why the spike? ….. The Anatomy of Neuroendocrine Cancer” 
  • Most blog views in one month: 19,303 in Apr 2017.  Why the spike? …. too many to list – see above!

Where did May 2017 Blog views come from? – Top 10 countries:  India on the up.

 

For interest. the 10 Ten Facebook followers by Country – Germany sneaking up.  Interestingly Canada reads more than Australia despite fewer followers.  India reads a lot!

 

WOW!  – that’s an amazing amount of awareness and hopefully, support for others.  However, I cannot do this without you guys liking, commenting and sharing!  The likes give me motivation, the comments (and private messages) give me inspiration (or at least a chance to explain further) and the sharing gives me a bigger platform.  A bigger platform generates more awareness.

Thanks for your great support in May.  Onwards and upwards!

Thanks for reading

Ronny

Hey, I’m also active on Facebook.  Like my page for even more news.

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Check out my Podcast (click and press play)

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

community_titled_transparent_2013-10-22

Don’t believe the hype – Neuroendocrine Cancer Myths debunked

Don't believe the hype - 10 myths

 

OPINION.

There’s a lot of inaccurate and out of date information out there.  Some is just a lack of understanding, often with a combination of patient forum myth spreading. Some can only be described as propaganda.

Myth 1:  All Neuroendocrine Tumours are benign

Not trueBy any scientific definition, the word ‘tumour’ means ‘an abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumours may be benign (not cancerous), or malignant (cancerous)’.  Sure, some NETs will be benign.  However, The World Health Organisation (WHO) 2010 classification for digestive system is based on the concept that all NETs have malignant potential, and has therefore abandoned the division into benign and malignant NETs and tumours of uncertain malignant potential.  This has been reinforced in the 2017 update to include clarification for other endocrine organ types of NET including Pheochromocytoma. Read more here.  The word ‘Carcinoid’ is inextricably linked with this issue – read here why we need to stop using the term to help fight the benign myth.

Kunz His belief these tumors did not metastisize

Myth 2:  Neuroendocrine Tumours is a terminal condition

Not true.  By any definition of the word terminal in a medical diagnostic context, most NET patients have a good prognostic outlook, even those with metastatic and incurable variants of the disease. Read more here.

being_there_front
Graphic courtesy of Ellie McDowell

Myth 3: Carcinoid is another word for Neuroendocrine Tumours 

Not true.  Carcinoid is a very old term and was phased out years ago.  Carcinoid is not mentioned in the latest WHO Classification schemes for Neuroendocrine Neoplasms (a term covering Neuroendocrine Tumours and Neuroendocrine Carcinoma). Unfortunately, the problem is exacerbated by organisations and individuals who still use the word.  Also, those who use the following terms:

  • “Carcinoid Neuroendocrine”,
  • “Neuroendocrine Carcinoid”,
  • “Carcinoid and Neuroendocrine”,
  • “Neuroendocrine and Carcinoid”,
  • “Carcinoid NETs” or “CNET”

These are all contextually incorrect and misleading terms (not to mention the bad grammar). ENETS, NANETS and NCCN publications are gradually phasing the word out except in relation to Carcinoid Syndrome (and even then there could be easy solutions for this). Read more here and here.

carcinoid vs neuroendocrine

Myth 4:  All NET patients get ‘carcinoid syndrome’

Not true.  Firstly, many NET cancers are non-functional; and secondly, carcinoid syndrome is only one of a number of “NET Syndromes” associated with the various types of NET. However, the issue is further confused by those who use the word ‘Carcinoid‘ to incorrectly refer to all NETs and use Carcinoid Syndrome to refer to all NET Syndromes.  Read more here.

Early signs of a late diagnosis (2)

Myth 5:  Neuroendocrine Neolasms are rare

Not true.  As a collective grouping of cancers, this is no longer accurate. Read more here.  Also check out my post about the “Invisible NET Patient Population“.

Yao not rare

Myth 6:  Steve Jobs had Pancreatic Cancer

Not true.  Steve Jobs had a Neuroendocrine Tumour of the Pancreas.  Ditto for a few other famous names. Read more here.

steve jobs 2010
The last few years have reminded me that life is fragile

Myth 7:  I’m not getting chemotherapy, I must be doing OK?

Not true.  For some cancers or some sub-types of cancers, although it remains an option, chemotherapy is not particularly effective, e.g. some types of Neuroendocrine Cancer (NETs). In general, well differentiated NETs do not normally show a high degree of sensitivity to chemotherapy, although some primary locations fare better than others. However, many of the treatments for NET Cancer are somewhat harsh, have long-term consequences, and have no visible effects. NET patients are often said to “look well” but that doesn’t mean they are not struggling behind the scenes or under the surface.  Read more here.  P.S. Afinitor (Everolimus), Sutent (Sunitinib) are not chemo – Read more here.

chemotherapy-hand-and-arm

Myth 8:  All diarrhea is caused by carcinoid syndrome

Not true.  It could be one of the other syndromes or tumor types or a side effect of your treatment.  Check out this post.

NETCancer Diarrhea Jigsaw

Myth 9:  Neuroendocrine Tumours is a ‘good cancer’

Not true.  Simply, no cancer is good.  Some are statistically worse than others in prognostic terms, that’s true…… but living with NETs is very often not a walk in the park. However, no one cancer is better to get than any other – they’re all bad.  Read more here.

Good-Bad

Myth 10:  Every NET Patient was misdiagnosed for years

Not true.  Many NET Patients are correctly diagnosed early on in their investigation and in a reasonable time.  This myth is perpetuated because of two things: firstly, on forums, the ratio of long-term misdiagnosis is high creating a false perception; and secondly, the method of capturing patient surveys is not extensive enough – again creating a false perception.  In fact, the latest and largest database analysis from US indicates earlier diagnosis is improving, with more and more NETs being picked up at an early stage. Read more here.

if your doctors dont suspect something

Myth 11:  Somatostatin Analogues are a type of Chemotherapy

Not true.  Somatostatin Analogues (e.g. Octreotide and Lanreotide) are not chemotherapy, they are hormone inhibiting drugs.  They are more biotherapy. As the drugs latch onto somatostatin receptors, they are more targeted than systemic. For the record, Everolimus (Afinitor) and Sunitinib (Sutent) are not chemotherapy either. Read more here.

chemo-or-not-chemo

Myth 12:  Stuart Scott (ESPN) and Audrey Hepburn had Neuroendocrine Cancer. 

Not true. This is a common misunderstanding within the community.  They both had Pseudomyxoma Peritonei (PMP).  Read more about PMP here.

 

 

 

Myth 13:  I’ve been diagnosed with Neuroendocrine Tumours – my life is over

Not true.  Many patients live a very long time and lead fairly normal lives with the right treatment and support. It’s difficult but I try not to use ‘I can’t’ too much. Read more here.

I CAN

Myth 14:  There are only a handful of Neuroendocrine specialists in the world

Not true.  There are many specialists in many countries. Get links to specialists by clicking here

find net specilaist and 10 qeusitons

 

Myth 15:  The Ga68 PET scan is replacing the CT and MRI scan in routine surveillance for all NET Patients

Not true.  It is actually replacing the Octreotide Scan for particular purposes,  or will eventually.  Read more by clicking here.

PET-CT-Scanner

Myth 16:  All NET Patients are Zebras

Not true.  They are in fact human beings and we should treat them as such. Please don’t call me a zebra, I and many others don’t appreciate it. Please don’t use the term on my social media sites, the comment or post will be removed.  Sorry but I refuse to perpetuate this outdated dogma. Read why here:

hoofbeats

Myth 17: Multiple Endocrine Neoplasia (MEN) is a type of Neuroendocrine Tumour

Not true. Multiple Endocrine Neoplasia are syndromes and inherited disorders not tumours.  You can actually have MEN and not have any tumours.  However, these disorders can put people at more risk of developing Neuroendocrine or Endocrine Tumours. Read more here

genetics

Myth 18: Palliative Care means end of life or hospice care  

Not true. Palliative care is specialized medical care that focuses on providing patients relief from pain and other symptoms of a serious illness. A multidisciplinary care team aims to improve quality of life for people who have serious or life-threatening illnesses, no matter the diagnosis or stage of disease. Read more here

The P word

Myth 19: Serotonin is found in foods

Not true. Serotonin is manufactured in the body. Read more here

brain-neurotransmitter-serotonin

Myth 20: NETs cannot be cured

Not true. If caught early enough, some NETs can be treated with curative intent (totally resected with margins) with little or no further follow up.  It says this in ENETS and NANETS publications which are authored by our top specialists. If we can’t believe them, who can we believe? Read more here.

cure quote

Myth 21: Pancreatic Enzyme Replacement Therapy (Creon etc) is only for pancreatic patients

Not true. It’s for any patient who is exhibiting exocrine pancreatic insufficiency. Read more here.

PERT

 

Myth 22: High Grade NETs are Carcinomas

Not entirely true.  Grade 3 (high grade) comprises well differentiated tumours and poorly differentiated tumours.  Only poorly differentiated tumour are carcinomas. Read more here.

High Grade

More to follow no doubt

For general cancer myths and the dangers of fake health news, please see my ARTICLE HERE

Thanks for reading

Ronny

Hey Guys, I’m also active on Facebook.  Like my page for even more news.  I’m also building up this site here: Ronny Allan

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Check out my Podcast (click and press play)

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients included

wego blog 2018 winner

Recent Progress in NET Management – Positive presentation from Jonathan R Strosberg MD

jonathan-strosbergI recently wrote a blog called Neuroendocrine Cancer – Exciting Times Ahead! I wrote that on a day I was feeling particularly positive and at the time, I wanted to share that positivity with you. I genuinely believe there’s a lot of great things happening. Don’t get me wrong, there’s a lot still to be done, particularly in the area of diagnosis and quality of life after being diagnosed. However, this is a really great message from a well-known NET expert.

In an interview with OncLive, Jonathan R. Strosberg, MD, associate professor at the H. Lee Moffitt Cancer Center in Florida, discussed his presentation on NETs at a recent 2016 Symposium, and shed light on the progress that has been made in this treatment landscape.

OncLive: Please highlight some of the main points from your presentation.

Strosberg: The question I was asked to address is whether we’re making progress in the management of NETs, and I think the answer is unequivocally yes. Prior to 2009, there were no positive published phase III trials.

Since then, there have been 8 trials, 7 of which have reached their primary endpoints. So it’s been a decade of significant improvement. And even though none of these studies were powered to look at overall survival as an endpoint, we’re certainly seeing evidence of improvement in outcomes.

OncLive: What are some of the pivotal agents that you feel have impacted the paradigm in the past several years?

Strosberg: The first group is the somatostatin analogs. We use them to control hormonal symptoms like carcinoid syndrome, but with the CLARINET study, we now know that they substantially inhibit tumor growth.

The next significant drug we use in this disease is everolimus (Afinitor), an oral mTOR inhibitor, which is now approved in several indications based on positive phase III studies. The first was in pancreatic NETs and subsequently, based on the RADIANT-4 trial, it was also approved in lung and gastrointestinal NETs. So that was an important advance.

The next important category of treatment is radiolabeled somatostatin analogs, otherwise known as peptide receptor radiotherapy. The one that’s been tested in a phase III trial is lutetium dotatate, also known as Lutathera. It was tested in patients with progressive midgut NETs and showed a very substantial 79% improvement in progression-free survival, and a very strong trend toward improvement in overall survival, which we hope will be confirmed upon final analysis.

OncLive: Are we getting better at diagnosing and managing the treatment of NETs?

Strosberg: Certainly. I think pathologists are better at making the diagnosis of a NET, rather than just calling a cancer pancreatic cancer or colorectal cancer. They’re recognizing the neuroendocrine aspects of the disease, and doing the appropriate immunohistochemical staining.

We also have better diagnostic tools. We used to rely primarily on octreoscan, and in many cases we still do, but there is a new diagnostic scan called Gallium-68 dotatate scan, also known as Netspot, which has substantially improved sensitivity and specificity. It’s not yet widely available, but it is FDA approved and hopefully will enable better diagnosis as well as staging in the coming years.

And, with the increase in number of phase III studies, we’re developing evidence-based guidelines, which will hopefully lead to more standardization, although knowing how to sequence these new drugs is still quite challenging.

OncLive: With sequencing, what are the main questions that we’re still trying to answer?

Strosberg: If we take, for example, NETs of the midgut, beyond first-line somatostatin analogs, physicians and patients often face decisions regarding where to proceed next, and for some patients with liver-dominant disease, liver-directed therapies are still an option.

For others, everolimus is a systemic option, and then hopefully lutetium dotatate will be an option based on approval of the drug, which is currently pending. Knowing how to choose among those 3 options is going to be a challenge, and I think there will be debates. Hopefully, clinical trials that compare one agent to another can help doctors make that choice. It’s even more complicated for pancreatic NETs. Beyond somatostatin analogs, we have about 5 choices—we have everolimus, sunitinib (Sutent), cytotoxic chemotherapy, liver-directed therapy, and peptide receptor radiotherapy. It’s even more challenging in that area.

OncLive: Are there any other ongoing clinical trials with some of these agents that you’re particularly excited about?

Strosberg: There’s a trial that is slated to take place in Europe which will compare lutetium dotatate with everolimus in advanced pancreatic NETs, and I think that’s going to be a very important trial that will help us get some information on both sequencing of these drugs, as well as the efficacy of Lutathera in the pancreatic NET population, based on well-run prospective clinical trials. I’m particularly looking forward to that trial.

OncLive: Looking to the future, what are some of the immediate challenges you hope to tackle with NETs?

Strosberg: One area of particular need is poorly differentiated neuroendocrine carcinomas. That’s a field that’s traditionally been understudied. There have been very few prospective clinical trials looking at this particular population, and we’re hoping that will change in the near future. There are a number of trials taking place looking at immunotherapy drugs. If these agents work anywhere in the neuroendocrine sphere, they are more likely to work in poorly differentiated or high-grade tumors, in my opinion, given the mutational profile of these cancers. So that’s something I’m particularly looking forward to being able to offer these patients something other than the cisplatin/etoposide combination that goes back decades, and is of short-lasting duration.

See more at: http://www.onclive.com/publications/oncology-live/2016/vol-17-no-24/expert-discusses-recent-progress-in-net-management#sthash.ypkilX2A.dpuf

Thanks for reading

Ronny

Hey Guys, I’m also active on Facebook.  Like my page for even more news.

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

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Neuroendocrine Tumor Drug Clinical Trial – Cabozantinib (includes news on Pheochromoctyoma and Paraganglioma)

What is Cabozantinib?

Cabozantinib is an oral drug which works by blocking the growth of new blood vessels that feed a tumour. In addition to blocking the formation of new blood cells in tumours, Cabozantinib also blocks pathways that may be responsible for allowing cancers cells to become resistant to other “anti-angiogenic” drugs. It is a type of drug called a growth blocker.  Cabozantinib has been studied or is already in research studies as a possible treatment for various types of cancer, including prostate cancer, ovarian cancer, brain cancer, thyroid cancer, lung cancer, and kidney cancer. During my research, I found that it has a connection to Medullary Thyroid Cancer (MTC) which is a type of Neuroendocrine Cancer, frequently associated with Multiple Endocrine Neoplasia (MEN).  Cabozantinib, under the brand name of ‘Cometriq’ was approved by the FDA in 2012 for use in MTC.  Read more about Cometriq here.  It’s also been approved by the FDA for advanced renal cell carcinoma (RCC) (branded as Cabometyx). I also discovered that there is an exclusive licensing Agreement with the manufacturers (Elelixis) and Ipsen (of Lanreotide fame) to commercialize and develop Cabozantinib in regions outside the United States, Canada and Japan

Growth blockers are a type of biological therapy and include tyrosine kinase inhibitors, proteasome inhibitors, mTOR inhibitors, PI3K inhibitors, histone deacetylase inhibitors and hedgehog pathway blockers.  Cabozantinib is a tyrosine kinase inhibitor (TKI).  They block chemical messengers (enzymes) called tyrosine kinases.  Tyrosine kinases help to send growth signals in cells so blocking them stop the cell growing and dividing.  Some TKIs can block more than one tyrosine kinase and these are known as multi-TKIs.

cabozantinib-picture
Example action of Cabozantinib

So Capozantinib is a tyrosine kinase inhibitor and is therefore a biological therapy and growth blocker just like Everolimus (Afinitor) and Sunitinib (Sutent) – some texts describe thelattero two as chemotherapy but this is just not accurate.

Very technical process but in the simplest of terms, Cabozantinib is designed to disrupt the actions of VEGF (a growth factor) and MET (a growth factor receptor) which promote spread of cancerous cells through the growth of new blood vessels.  Whilst we are on this subject, please note Everolimus (Afinitor) is an mTOR inhibitor and Sunitinib (Sutent) is a tyrosine kinase inhibitor. Many people think these drugs are a type of chemo – that is incorrect, these are targeted biological therapies.  See more on this by clicking here.

What is the current trial status of Capozantinib?

A Phase III trial is now recruiting entitled Cabozantinib S-malate in Treating Patients With Neuroendocrine Tumors Previously Treated With Everolimus That Are Locally Advanced, Metastatic, or Cannot Be Removed by Surgery”. 

The trial has 172 locations across the US (see link below). The primary study (final data) is scheduled Jan 1st 2021.

You can read the trial documentation by clicking here.

Progress report

  1. Poster submission for 2017 Gastrointestinal Cancer Symposium
  2. Onc Live output from the 2017 Gastrointestinal Cancer Symposium
  3. Output from NANETS 2017
  4. A funded piece of research by the NET Research Foundation – check it out herelooks like they are trying to figure out what patients might benefit from Cabozantinib using biomarker data to predict response.
  5. Dr Jennifer Chan speaking in 2018 about the drug potential.  (Apologies for the use of the out of date term ‘Carcinoid‘).
  6. Phase 3 Clinical Trial Document – click here

————————-

UPDATED 2018 – There’s also another trial looking at unresectable metastatic Pheochromocytomas and Paragangliomas

A Phase 2 Study to Evaluate the Effects of Cabozantinib in Patients with Unresectable Metastatic Pheochromocytomas and Paragangliomas 

This part is from an article collaboration between MedPage Today® and the American Association of Clinical Endocrinologists

BOSTON — Cabozantinib (Cabometyx) may benefit patients with malignant pheochromocytomas and paragangliomas, according to results of a phase II trial presented here.

Patients receiving cabozantinib (Cometriq) treatment experienced notable tumor shrinkage in the lymph nodes, liver, and lung metastases, according to Camilo Jimenez, MD, of the MD Anderson Cancer Center in Houston, and colleagues.

Additionally, progression-free survival significantly increased after treated to 12.1 months (range 0.9-28) compared with just 3.2 months prior to treatment, they reported at the American Association of Clinical Endocrinologists (AACE) annual meeting.

Cabozantinib treatment was also tied to an improvement in blood pressure and performance status, as well as remission of diabetes among these patients.

“Malignant pheochromocytomas and paragangliomas are frequently characterized by an excessive secretion of catecholamines. [Patients] have a large tumor burden and they have a decreased overall survival,” explained Jimenez. “Tumors are frequently very vascular and frequently associated with bone metastases. In fact, up to 20% of patients who have malignancy of pheochromocytomas and paragangliomas may have predominant bone metastases.”

He added that “an interesting aspect of this tumor is that C-MET receptor mutation have been found in occasional patients with malignant pheochromocytomas and paragangliomas.”

Cabozantinib is an anti-angiogenic tyrosine kinase inhibitor, which also targets RET, MET, and AXL. It is approved for metastatic medullary thyroid cancer, and was more recently approved for first-line treatment of advanced renal cell carcinoma.

“MET pathway is also involved in the development of bone metastases. In fact, cabozantinib is a very effective medications for patients who have bone metastases in the context of cancer of different origins,” Jimenez said.

In order to be eligible for the trial, patients with confirmed pheochromocytoma or paraganglioma had to be ineligible for curative surgery, have ≥3 months life expectancy, no risk for perforation or fistula, and adequate organ functioning. Prior to cabozantinib initiation, patients could not receive chemotherapy or biologic agents within 6 weeks, radiation within 4 weeks, or MIBG within 6 months.

Following histological confirmation of disease progression >1 year according to RECIST 1.1, the trial included 14 patients with measurable disease and eight patients with predominant/exclusive bone metastases. Fifteen patients subsequently enrolled into the trial, six of whom had germline mutations of the SDHB gene.

All participants were all started at an initial daily dose of 60 mg of cabozantinib, which was subsequently reduced down to between 40 to 20 mg due to toxicity in 13 patients based on tolerance.

The majority of these patients with measurable disease experienced some level of disease response. Six patients reported a partial response, defined as over a 30% reduction, while three patients achieved moderate response, marked by a 15%-30% reduction. Five of the patients with predominant bone metastases reported disease stabilization, according to results of an FDG-PET scan. One patient experienced disease progression while on treatment.

Overall, cabozantinib was generally well-tolerated without any grade 4 or 5 treatment-related adverse events reported. Some of the most common adverse events reported included grade mild dysgeusia, hand and foot syndrome, mucositis, fatigue, weight loss, and hypertension, according to the authors.

  • Primary Source – American Association of Clinical Endocrinologists meeting – AACE 2018; Abstract 142. attended my Medscape writers

You can see the Pheo/Para clinical trial document by clicking here.

————————————–

Summary

I generated this blog article to add value rather than just post the outputs for your own perusal.  I hope you find it useful.

Please note that taking part in a clinical trial is a big decision and must be considered carefully in conjunction with your specialists if necessary.  This article is not suggesting this trial is right for you.  Please check the inclusion and exclusion criteria in the trials document carefully. (Pheo/Para patients see other clinical trial link above)

Chemo or not Chemo – that is the question 


I’m continually seeing certain drugs for treatment of Neuroendocrine Tumours (NETs) described as chemotherapy. I think there must be some confusion with more modern drugs which are more targeted and work in a different way to Chemotherapy.

I researched several sites and they all tend to provide a summary of chemotherapy which is worded like this:  Chemotherapy means:

a treatment of cancer by using anti-cancer medicines called cytotoxic drugs.  Cytotoxic medicines are poisonous (toxic) to cancer cells. They kill cancer cells or stop them from multiplying. Different cytotoxic medicines do this in different ways. However, they all tend to work by interfering with some aspect of how the cells divide and multiply. Two or more cytotoxic medicines are often used in a course of chemotherapy, each with a different way of working. This may give a better chance of success than using only one. There are many different cytotoxic medicines used in the treatment of cancer. In each case the one (or ones) chosen will depend on the type and stage of your cancer. Interestingly, there are several statements along the lines of ‘Cytotoxic medicines work best in cancers where the cancer cells are rapidly dividing and multiplying’, a key issue with lower grade NETs.

Well known chemotherapy treatments for NETs include (but are not limited to): Capecitabine (Xeloda), Temozolomide (Temodal), Fluorouracil (5-FU), Oxaliplatin (Eloxatin) Cisplatin, Etoposide (Etopophos, Vepesid), Carboplatin, Streptozotocin (Zanosar). Some of these may be given as a combination treatment, e.g. CAPecitabine and TEMozolomide (CAPTEM).

In the past, any medication used to treat cancer was regarded as chemotherapy. However, over the last 20 years, new types of medication that work in a different way to chemotherapy have been introduced. Many of these new types of medication are known as targeted therapies. This is because they’re designed to target and disrupt one or more of the biological processes that cancerous cells use to grow and reproduce.  They are classed as biological therapy.  In contrast, chemotherapy medications are mostly systemic in nature and designed to have a poisonous effect on cancerous cells, thus the term ‘cytotoxic’.

The following well known NETs treatment are not really chemotherapy and describing them in this way is not only misleading but may actually cause alarm to other patients. Furthermore, if you check any authoritative NET Cancer specialist or advocate organisation; any general and authoritative cancer site or the manufacturer’s websites; you will not see the drugs below listed within the term chemotherapy.

Somatostatin Analogues e.g. Sandostatin (Octreotide), Somatuline (Lanreotide).  Although these drugs have an anti-cancer effect for some, they are in fact hormone inhibitors and are therefore a hormone therapy.

Everolimus (Afinitor).  This is a targeted biological therapy or more accurate a mammalian target of rapamycin (mTOR) inhibitor. It is a type of treatment called a signal transduction inhibitor. Signal transduction inhibitors stop some of the signals within cells that make them grow and divide. Everolimus stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus helps to stop the cancer growing or may slow it down.

Sunitinib (Sutent).  This is a targeted biological therapy or more accurate a protein (or tyrosine) kinase inhibitor. Protein kinase is a type of chemical messenger (an enzyme) that plays a part in the growth of cancer cells. Sunitinib blocks the protein kinase to stop the cancer growing. It can stop the growth of a tumour or shrink it down.

I can only speculate why some of the confusion exists but I do have some personal experience I can quote too. Firstly I believe it could be easier for some people to describe the new agents as ‘chemotherapy’ rather than explain things such as somatostatin analogues, ‘mammalian target of rapamycin (mTOR) inhibitors’, protein kinase inhibitor or angiogenesis inhibitors. Another reason could be that health insurance companies do not have the correct database structures in place on their IT systems and therefore need to ‘pigeon hole’ drugs into the closest category they can see. Often this is chemotherapy and this only adds to the confusion. In the days when I had health insurance, my Lanreotide injections were coded as chemotherapy on all my bills. I challenged it and this is how they explained the issue.

I’m sure there’s other reasons.

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Neuroendocrine Cancer – Exciting Times Ahead!  

exciting-times-ahead_edited

In the last 12-24 months, there seems to have been announcement after announcement of new and/or upgraded/enhanced diagnostics and treatment types for Neuroendocrine Cancer.  Scans, radionuclide therapies, combination therapies, somatostatin analogues, biological therapies, etc.  Some of the announcements are just expansions of existing therapies having been approved in new (but significant) regions. Compared to some other cancers, even those which hit the headlines often, we appear to be doing not too badly.  However, the pressure needs to stay on, all patients need access to the best diagnostics and treatments for them; and at the requisite time.  There’s even more in the pipeline and I’m hoping to continue to bring you news of new stuff as I have been doing for the last year.

Some of these new diagnostics and treatments will benefit eligible patients who are in diagnosis/newly diagnosed and also those living with the disease. As we’re now in our awareness month, let’s recap:

Scans

Many NET Patients will undergo a nuclear scan to confirm CT results and/or to detect further neuroendocrine activity.  Basically, a nuclear substance is mixed with a somatostatin analogue, injected into the patient who is then scanned using a 360-degree gamma camera.  As gamma cameras are designed to show up radioactive activity; and as Neuroendocrine Tumour cells will bind to the somatostatin analogue, it follows that the pictures provided will show where Neuroendocrine tumours are located.  Many people will have had an ‘Octreotide’ Scan (or more formally – Somatostatin Receptor Scintigraphy) which is still the gold standard in many areas. The latest generation of nuclear scans is based on the platform of the Gallium (Ga) 68 PET Scan. The principles of how the scan works is essentially as described above except that the more efficient radioactive/peptide mix and better scan definition, means a much better picture providing more detail (see example below). It’s important to note that positive somatostatin receptors are necessary for both scans to be effective. Europe and a few other areas have been using the Ga-68 PET scans for some time (although they are still limited in availability by sparse deployment). The latest excitement surrounding this new scan is because they are currently being rolled out in USA.  Read about the US FDA approval here.  You may hear this scan being labelled as ‘NETSPOT’ in USA but this is technically the name for the preparation radiopharmaceutical kit for the scan which includes a single-dose injection of the organic peptide and the radionuclide material. Take a look at a comparison of both scans here:

octreo-vs-g68
Octreoscan output vs Gallium 68 PET output

This slide from a recent NET Research Foundation conference confirms the power of more detailed scanning.

Peptide Receptor Radionuclide Therapy (PRRT)

Similar to above, this treatment has been in use in Europe and other places for some time but is also to be formally deployed in USA if, as is expected, the US FDA approval is positive at the end of this year (Read here).  In the most basic terms, this is a treatment whereby a peptide is mixed with a radionuclide and is drip fed over a number of treatments (normally up to 4 spaced out over a year). The concept of delivery of the ‘payload’ to the tumours is actually very similar to the preparation for a radionuclide scan as described above, the key difference is the dosage and length of exposure whilst the tumours are attacked. Once again, receptors are important. The NETTER series of trials showed good results and this is an excellent addition to the portfolio for those patients who are eligible for this treatment. Fingers crossed for the US FDA announcement due by the end of this year.  Also fingers crossed that PRRT returns to the NHS England & Wales portfolio of available treatments next year.  The Carcinoid Cancer Foundation has an excellent summary of PRRT here.

PRRT and Chemo Combo

Whilst on this subject, I also want to highlight the innovative use of combo therapies in Australia where they are combining PRRT and Chemo (PRCRT).  I blogged about this here:

PRRT CAPTEM

Somatostatin Analogues and their Delivery Systems

Somatostatin analogues are a mainstay treatment for many NET Patients.  These drugs target NET cell receptors which has the effect of inhibiting release of certain hormones which are responsible for some of the ‘syndromic’ effects of the disease.  Again, receptors are important for the efficacy of this treatment.  You can read the ‘geeky’ stuff on how they work here.  These drugs mainly comprise Octreotide (provided by Novartis) and Lanreotide (provided by Ipsen). The latter has been around in Europe for 10 years and was introduced to North America earlier this year.  Octreotide has been around for much longer, almost 17 years.  When you consider these peptides have also been used to support nuclear scans that can detect the presence of tumours; and that studies have shown they also have an anti-tumour effect, they really are an important treatment for many NET Patients.  I’ve blogged about new somatostatin analogues in the pipeline and you can read this here.  This blog also contains information about new delivery systems including the use of oral capsules and nasal sprays (…….. very early days though).

Treatment for Carcinoid Syndrome

telotristat-etiprate-clinical-trial-serotonin-as-a-key-driver-of-carcinoid-syndrome

For maintenance and quality of life, the release of a Telotristat Ethyl for Carcinoid Syndrome is an exciting development as is the first new treatment for Carcinoid Syndrome in 17 years.  This is a drug which is taken orally and inhibits the secretion of serotonin which causes some of the symptoms of the syndrome including diarrhea.  It must be emphasised it’s only for treating diarrhea caused by syndrome and might not be effective for diarrhea caused by other factors including surgery.  Read about how it works and its target patient group in my blog here.

Oncolytic Virus

oncolytic

The announcement of a clinical trial for the Oncolytic Virus (an Immunotherapy treatment) specifically for Neuroendocrine Tumours is also very exciting and offers a lot of hope. Click the photo for the last progress update.  

Everolimus (Afinitor)

013490_PNETUS_iPad_pg2v2

Earlier this year, AFINITOR became the first treatment approved for progressive, non-functional NETs of lung origin, and one of very few options available for progressive, non-functional GI NET, representing a shift in the treatment paradigm for these cancers.  It’s been around for some time in trials (the RADIANT series) and is also used to treat breast and kidney cancer.  It’s manufactured by Novartis (of Octreotide fame).  It has some varying side effects but these appear to be tolerable for most and as with any cancer drug, they need to weighed against the benefits they bring.

In technical terms, AFINITOR is a type of drug known as an ‘mTOR’ inhibitor (it’s not a chemo as frequently stated on NET patient forums).  Taken in tablet form, it works by blocking the mTOR protein. In doing so, AFINITOR helps to slow blood vessels from feeding oxygen and nutrients to the tumour.

Check out Novartis Afinitor website for more detailed information.  There’s an excellent update about AFINITOR rom NET expert Dr James Yao here.  The US FDA approval can be found here.

Summary

………. and relax!   Wow, I’ve surprised myself by collating and revising the last 12-24 months.  Dr James Yao also agrees – check out his upbeat message in the attached 2 page summary.  You may also like another upbeat message from Dr Jonathan Strosberg by clicking here.

Neuroendocrine Cancer – who’d have thought it?  ….. a bit of a dark horse.

Thanks for reading

Ronny

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community_titled_transparent_2013-10-22

 

Living with Neuroendocrine Cancer – it takes guts

it-takes-guts-living-with4.jpg

The majority of Neuroendocrine Tumours (NETs) are slow-growing (well differentiated).  However, many tumours can be silent (non-functioning) for some years before they start to ‘function’ and inform you of their presence.  Even then, it may take some time to work out the real cause as the symptoms can mimic regular ailments.  Moreover, in most cases, the appearance of a functional tumour normally indicates the disease has metastasized and could now be incurable. Some tumours will grow and metastasize without syndromes, i.e. they are non-functional. These may become functional at some point in the future.

However, with most slow-growing NETs, this does not mean terminal as there are various treatment options even at Stage IV.  In fact, NETs are one example where surgery at the metastatic stage can often provide prognostic advantages denied in other more aggressive types of cancer at the same stage.  However, it’s true to say that many NET patients regardless of tumour type or grade and stage of tumour, need to live with quality of life (QoL) challenges.

I sense a change of thinking about people living longer with cancer and the reasons are fairly obvious.  Due to better diagnostics and treatment (including for NETs), more people are now living with their cancer; and as a species were are actually living longer. Add the two together and you can see why the big charity organisations are now saying that one in two people will develop cancer at some point in their lives. Ergo – as we live longer we are more likely to come into contact with cancer on the basis that age is a big factor whether someone gets it or not. Now that sounds pessimistic but this needs to be put into context. For example, in UK today, more than one in three (35%) of those people who die having had a cancer diagnosis will now die from other causes. This is up from one in five (21%) 20 years ago. By 2020 this will improve further to almost four in 10 people (38%).  This means the number of people who get cancer but die from another cause has doubled over the past 20 years. According to Macmillan Cancer, the cancer story is changing. What was once feared as a death sentence is now an illness that many people surviveA small bit of research indicates this type of thinking is becoming more apparent in other countries too. As survival rates increase, so too will the number of people living with the legacy of cancer and its treatment.

HOWEVER!

Although more people are living with cancer rather than dying from it, quality of life must be a factor going forward.   Any quality of life campaign fits nicely into the existing challenges faced by many Neuroendocrine Cancer patients who need support well beyond their diagnosis and treatment and for some time.

I consider these campaigns additional help in fighting our corner.  And of course we need help because for many NET patients there will be no remission, there will be no cure.  Cancer patients need more support after a cancer diagnosis.  NET patients are effectively already in this position and have been for some time.  We have been at the forefront of a group of people living with cancer and needing close support and surveillance.  For example:

Late diagnosis. People will be dealing from the effects of late diagnosis which has resulted in metastatic disease –  and some people will have been fighting misdiagnosed illnesses for years.  That takes its toll.

Consequences of Surgery. People will have had surgery which in many cases is life changing – various bits of the gut (gastrointestinal tract) are now missing, lungs are now missing – many other locations will have been excised or partly excised.  These bits of our anatomy were there for a reason and QoL takes a hit when they are chopped out. Many patients succumb to gastrointestinal malabsorption

Inoperable Tumours and Syndromes. People will be dealing with remnant and/or inoperable tumours which may or may not be producing an associated NET syndrome (some of the symptoms can be rather debilitating in the worst cases)

Consequences of Non-surgical Treatment.  Additionally, people will be dealing with the side effects of multi-modal non surgical treatments, such as somatostatin analogue hormone therapy (Octreotide/Lanreotide), chemotherapy, biological therapy (mTOR inhibitors) (i.e. Everolimus (Afinitor)), biological therapy (protein kinase inhibitors (i.e. Sunitinib (Sutent)), radionuclide therapy (i.e. PRRT).  Whilst it’s great there are a wide range of therapies, they all come with side effects.

Secondary Illnesses and Comorbidities. Some people will have gained secondary illnesses in part due to the original cancer or treatment – i.e. somatostatin analogue hormone therapy can have a side effect of increasing blood sugar to diabetic levels and reduce thyroid function.  There are many other examples.

Finances. NET Cancer can be an expensive cancer to treat and this is exacerbated by the length of time the treatment lasts.  Whilst people have access to free public services or private insurance, many people will end up out-of-pocket due to their cancer.  Over time, this adds up.

Emotional Aspects. Many NET patients are kept under surveillance for the remainder of their lives.  With that comes the constant worry that the cancer progresses, tumours get bigger, new tumours show up, treatments are denied (i.e. PRRT in the UK).  It’s no surprise that anxiety and depression can affect many patients in these situations. To some extent, there can be a knock-on effect to close family members and carers/caregivers where applicable.

Living with Neuroendocrine Cancer is not easy – it takes guts (both metaphorically and literally).

Awareness of the issues surrounding diagnosis is important and remains so.  However, I believe more focus should be placed on support for those living with Neuroendocrine Cancer and it’s consequences.  So …. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for quality of life

Remember – they are no longer rare.

Thanks for reading

Ronny

I’m also active on Facebook.  Like my page for even more news.  I’m also building up this site here: Ronny Allan

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!


 

Somatostatin Analogues and delivery methods in the pipeline

As most of you will be aware, there are currently two main types of Somatostatin Analogues (SSA) in use for the treatment of mainstream Neuroendocrine Tumours (NETs) – Octreotide and Lanreotide. You can click on the links for information on both of these well-known NET treatments. This post will focus on the not so well known and anything in the pipeline including different delivery systems.

This is my live blog post covering new developments in the area of new Somatostatin Analogues and new delivery systems. 

Abstract

As most of you will be aware, there are currently two main types of Somatostatin Analogues (SSA) in use for the treatment of mainstream Neuroendocrine Tumours (NETs) – Octreotide and Lanreotide.  You can click on the links for information on both of these well-known NET treatments.  This post will focus on the not so well known and anything in the pipeline including different delivery systems.

Those who have read the Octreotide/ Lanreotide patient leaflets will know those SSAs are also used in the treatment of a condition known as Acromegaly. You can see why the drug is used for both as they control the release of excess secretions of various substances, a problem that has an effect on both conditions. In the case of Acromegaly, the condition is typically caused by pituitary tumours that oversecrete the growth hormone leading to elevated levels of IGF-1. Like NETs, Octreotide/Lanreotide is currently the mainstay non-surgical treatment for this condition. For those not aware of Acromegaly there is a nice infographic explaining it here.   

Delivery methods discussed in this post include: a smaller, faster and easier Octreotide injection, an Octreotide capsule, an Octreotide nasal spray.  Other somatostatin analogues includes Pasireotide which has already been approved for Cushing’s Syndrome and Acromegaly (core NET possibilities have been investigated) and a new kid in the pipeline called Veldreotide for Acromegaly but potential additional applications in Cushing’s syndrome and neuroendocrine tumors. Finally for those with an interest in Cushings, a drug currently in phase 3 trials called RECORLEV™ (Levoketoconazole) which is not actually a somatostatin analogue, rather it’s a cortisol synthesis inhibitor.

It’s important to understand that NETs and other conditions including Cushings and Acromegaly, very often share the same hormone inhibiting drugs, thus why any development for these type of drugs is of interest to all physicians and patients in the associated conditions.

It’s also useful to understand that many of these drugs/delivery mechanisms are driven by availability of funding and are subject to the vagaries of the market. One entry on the previous version of this article has been removed as the company manufacturing it went into administration (Solid Dose Injections).

Somatostatin Analogues – New Delivery Methods in the Pipeline

Crinetics Pharmaceuticals Initiates Phase 1 Study of CRN01941 for the Treatment of Neuroendocrine Tumors

Updated 21 May 2019.  Click here to read about this exciting development.

 

New delivery system for Octreotide LAR – “Q-Octreotide” (MDT201)

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MTD201 (Q-Octreotide)

Updated 20 Dec 2018.

An unnamed ‘pharma giant’ has signed a deal with Midatech Pharma Plc that will see it evaluate the latter’s Q-Sphera drug delivery platform.  Only a guess from me, but I suspect it’s either Novartis or Ipsen.

Midatech’s Q-Sphera™ is an advanced microencapsulation and polymer-depot sustained release (SR) drug delivery platform produced using a novel and disruptive printing based process, with numerous and distinct advantages over conventional reactor based technologies. From a manufacturing perspective Q-Sphera™ is a precise, scalable, efficient, and environmentally friendly microparticle platform. From a clinical perspective Q-Sphera™ ensures monodispersed microparticles that release active drug compounds into the body in a superior linear tightly controlled and predictable manner over an extended period of time from 1 – 6 months.  An injection lasting 6 months sounds very exciting but I have no more detail on the feasibility or likelihood of such a change in frequency with Octreotide or Lanreotide but the press release does mention the possibility, i.e. “Q-Sphera allows drug compounds to be released into the body in a “highly controlled manner” over a prolonged period of time; potentially from a few days to up to six months.”

What’s the main differences?

The current trials are based on the use of Sandostatin LAR (Octreotide) using the Q-Sphera delivery system (previously known as Q-Octreotide). The key aspects of usability are reconstitution and needle size but there is also an inference that less frequent injections could be possible.

Apparently, the delivery method (see picture) is smaller, faster, easier with the possibility of less frequent injections. More to follow when known but in the meantime, please see a useful Video about Q-Octreotide. Apologies for the use of the out of date term ‘carcinoid‘.

New Octreotide Delivery Method – Chiasma Capsule

mycappsa
Octreotide Capsules? Graphic from http://www.chiasmapharma.com/

Updated 14 Dec 2017. Acromegaly appears to be in the lead in terms of new delivery methods.  A pharma company called Chiasma is working on an oral version of Octreotide for this condition and they are currently at Phase 3 trials.   You can check out the technology here.

Clearly, we want drugs to be safe and the announcement is another reminder of why drugs take so long to be approved.  Chiasma’s investigational oral octreotide uses their proprietary TPE® (Transient Permeability Enhancer) technology to facilitate gastrointestinal absorption of the unmodified drug into the bloodstream safely (i.e. it keeps the drug safe until it reaches its destination).  Hopefully, the new trial can convince the FDA to finally approve.  The trial is currently only Acromegaly based and details are here.

This is potentially an exciting development given that both conditions use the same drugs (Octreotide and Lanreotide injections) so there is always the hope that NETs might be next in line if the capsule version is finally approved.  However, still very early days as the company does not anticipate the release of top line date from the Phase 3 trial until 2020. 

Intranasal administration of Octreotide Acetate 

intravail
Nasal Spray Octreotide?

Updated 14 May 2017.  Dauntless Pharmaceuticals, Inc., a privately held biopharmaceutical company focused on the development of specialty therapeutics, announced the outcome of a Phase 1 clinical study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of DP1038, a novel formulation of octreotide acetate for intranasal administration, compared to subcutaneous Sandostatin® (octreotide acetate) injection in healthy volunteers.  DP1038 (octreotide acetate for intranasal administration) is being developed via the 505(b)(2) regulatory pathway for the treatment of acromegaly and neuroendocrine tumors.  DP1038 leverages patented technology for enhanced intranasal absorption developed by Aegis Therapeutics, LLC, a drug delivery and drug formulation company that has successfully licensed its technology to leading pharmaceutical and biopharmaceutical companies whose partners have multiple late stage clinical programs under development. The drug will most likely use an administration system patented by Aegis called Intravail® Aegis Therapeutics LLC announced last year that it has been awarded U.S. Patent No. 9,446,134 providing non-invasive metered nasal spray delivery of Octreotide (click here to view the announcement). The enabling Aegis Intravail formulation technology is broadly applicable to a wide range of small molecule and biotherapeutic drugs to increase non-invasive bioavailability by the oral, nasal, buccal, and sublingual routes and to speed attainment of therapeutic drug levels in cases where a non-invasive (i.e., non-injectable) form of the drug is unavailable or where speed of onset is important.  A description of Intravail delivery systems can be found by clicking here.

About the Phase 1 Trial
The Phase 1 trial was designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of DP1038, a novel formulation of octreotide acetate for intranasal administration, compared to subcutaneous Sandostatin® (octreotide acetate) Injection in healthy volunteers. In Part 1 of the study, each of 12 subjects received three doses of DP1038 plus 100 micrograms of subcutaneous octreotide acetate in a randomized 4 x 4 Latin square design. DP1038 was well tolerated across all doses and demonstrated a consistent, dose-proportional pharmacokinetic profile with significant nasal bioavailability. In Part 2 of the study, a single dose of DP1038, which was selected to exhibit a similar pharmacokinetic profile to subcutaneous octreotide acetate, was evaluated in 20 subjects in a cross-over design to compare the pharmacodynamic effect to 100 micrograms of subcutaneous octreotide acetate. Subjects were given a GHRH-arginine challenge, a standard test to stimulate growth hormone release, followed by administration of DP1038 or subcutaneous octreotide acetate. DP1038 showed comparable growth hormone suppression to the subcutaneous reference product. The news announcing the output from the Phase 1 clinical trial can be found by clicking here. Clearly, this is very early days and the product would need to go through the normal drug approval and acceptance routes etc.  However, a Phase 1 trial using patients is very exciting.

New Somatostatin Analogues in the Pipeline

New Somatostatin AnaloguePasireotide

signiforlar-22

Updated 14 Dec 2017.  Not really new but I wanted to include it because it’s not very well-known. Pasireotide is also known as Signifor and SOM230.  This drug is already in the pipeline but only for Acromegaly and Cushing’s Syndrome.  I found it interesting that is able to function as a multireceptor-targeted SSA by binding with high affinity to 4 of the 5 somatostatin receptors (sstrs 1, 2, 3 and 5), with the highest affinity for sstr5, resulting in inhibition of adrenocorticotropic hormone (ACTH) secretion (Octreotide only binds to sstrs 2, 3 and 5). In fact, Signifor represents the first specific treatment for ACTH-secreting pituitary adenomas.  Moreover, it is the first approved medical treatment for Cushing’s disease.  If you’ve read my blog on NET Syndromes, you will see the connection – both involve pituitary tumours and this drug is designed to cater for scenarios where surgery has not solved the problem or is not an option. Interestingly Novartis describes it as a second generation SSA, inferring that Octreotide is first generation.  It comes in short and long acting (LAR) forms with a similar delivery system to Octreotide. It is a US FDA approved orphan drug and is also approved for use in the EU.  Novartis has also submitted additional regulatory applications for Signifor LAR worldwide.   You can read more by clicking here

However, there have been studies in its use for advanced NETs where Octreotide is not working or has not sufficiently controlled the effects of the syndrome.  You can read a full text article about the study results by clicking here (you will recognise some of the authors including Edward M Wolin, Christos Toumpanakis, John Ramage, Kjell Öberg).  My interpretation of the trial conclusion is that there does not appear to be any significant advantages of Pasireotide over Octreotide.  The attachment also confirmed studies are ongoing including a potential combination treatment of Pasireotide and Everolimus (Afinitor).  There does not appear to be a study comparing it to Lanreotide.

Jonathan R. Strosberg, MD, associate professor at H. Lee Moffitt Cancer Center, discussed pasireotide as a potential treatment for patients with neuroendocrine tumors (NETs). He said “Pasireotide is a somatostatin analog similar to octreotide (Sandostatin) and lanreotide (Somatuline). However, pasireotide targets 4 out of the 5 somatostatin receptor subtypes, which may provide it with an advantage over the other 3 agents. Thus far, there has not been enough evidence showing that pasireotide has a progression-free survival benefit over the other 2 therapies. It is also associated with hyperglycemia. Pasireotide may be an appropriate choice for patients in later lines of therapy. In the future, he envisions that patients could be selected for therapy based on their somatostatin receptor profile.”

New Somatostatin Analogue  – Veldoreotide (COR-005)

Updated 14 Dec 2017. There is another new drug in the pipeline currently known as Veldoreotide or COR-005 (although I can see the term ‘Somatoprim’ used on other searches). COR-005 is an investigational SSA in phase 2 development for treatment of patients with Acromegaly. Although the page on the manufacturer’s website does not mention NETs, an announcement of its progress has just been made at the Endocrine Society’s annual conference for 2016. The announcement states that the drug has “potential additional applications in Cushing’s syndrome and neuroendocrine tumors”.  COR-005 targets somatostatin receptors 2, 4 and 5. Read about the drug here.

COR-005 has received orphan drug designation (only for Acromegaly) in the US and EU. There is not enough data to understand how this might benefit NETs and what the differences would be.  Hopefully, an update will be available later which will result in an update to this post.

For those interested in Cushing’s Syndrome, (hypercortisolism or high levels of cortisol), the same manufacturer working on Veldoreotide is also working on a new drug in Phase 3 trials known as RECORLEV™ (Levoketoconazole). Not actually a somatostatin analogue, rather it’s a cortisol synthesis inhibitor

Summary

This information is provided for information only.  There is no intent to indicate at this point that these new drugs will eventually be approved for NETs.  However, it’s another indication that people are working on new treatments which might end up being available at some stage.

The pipeline for new treatments and methods of delivery continues to grow!

Thanks for reading

Ronny

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Clinical Trial: Neuroendocrine Cancer drug in the pipeline – Fosbretabulin Tromethamine CA4P (incl combo with Everolimus)

vda-video
Click this picture to see how VDAs work

{NEW} added 4 June 2019

From ASCO 2019 conference extract: Of the 17 patients enrolled, 16 completed the 12-week trial. One patient was not evaluable due to noncompliance. No DLTs were observed at day 21. The highest dose of 10 mg daily oral everolimus in combination with weekly 60mg/m2 IV fosbretabulin is the RP2D. No grade 4 or 5 toxicities were noted. Grade 3 toxicities were seen in 5 patients; abdominal pain and hyperglycemia (not related to study drug), fatigue (possibly related), decreased lymphocyte count and anemia (related). Several patients had delay in treatment due to grade 2 AE’s (GI symptoms, rash, thrombocytopenia) and one patient was unable to complete treatment due to pneumonitis. All evaluable patients except one had stable disease at 3 months. One patient showed SD but non target lesion demonstrated PD. One patient had > 30% decrease in tumor size but overall sum of lesions showed SD. A detailed table with all grade toxicities and waterfall plot of RR will be presented at the meeting. Ten mg PO daily everolimus plus 60 mg/m2 fosbretabulin IV weekly is the RP2D. Early clinical data suggests clinical activity and stable disease in all but one patient at 3 months. Read full text from ASCO 2019 here.

For further information about the clinical trial, please visit www.clinicaltrials.gov, Study NCT03014297

I will get a better picture but this is what they tweeted from ASCO 2019

markey trial


added 19 Apr 2017

Mateon Therapeutics, Inc. a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, today announced that the Markey Cancer Center at the University of Kentucky has enrolled the first patient into a new phase 1 study of CA4P in combination with everolimus for the treatment of neuroendocrine tumors.

“The combination of CA4P and everolimus has the potential to decrease the ability of tumor cells to recover between CA4P treatment cycles,” stated Lowell B. Anthony, M.D., Professor of Medicine and Chief, Division of Medical Oncology, Markey Cancer Center, University of Kentucky. “This is the first trial testing this hypothesis in neuroendocrine tumors – with CA4P disrupting the existing tumor blood supply and everolimus preventing a new tumor blood supply from re-forming. Our findings from this trial should lead to a larger clinical study once we have identified the optimal dose and schedule for the combination of these two agents.”

Study MCC-2016-088 is designed to demonstrate whether the addition of CA4P to everolimus may improve tumor control without additional toxicity. Everolimus has been approved by the U.S. Food and Drug Administration for the treatment of advanced pancreatic neuroendocrine tumors and progressive gastrointestinal neuroendocrine tumors, among other indications, and is marketed by Novartis under the tradename AFINITOR®. Mateon has previously demonstrated initial evidence of efficacy for CA4P in patients with neuroendocrine tumors when CA4P was provided as a single agent.

Study MCC-2016-088 is being sponsored, funded, and conducted by the Markey Cancer Center, with Mateon providing the investigational drug. The study is designed as a single center, open label, phase 1 clinical trial for patients with grade 1-3 gastroenteropancreatic neuroendocrine tumors. In the first part of the study, up to 15 patients will be treated with everolimus in combination with two different dosing regimens of CA4P to establish appropriate CA4P dosing levels and evaluate the safety of the drug combination.  The second part of the study is designed to enroll 15 additional patients for assessment of additional safety and efficacy data. Patients enrolled in MCC-2016-088 will be treated with CA4P and everolimus for 12 weeks.

For further information about the clinical trial, please visit www.clinicaltrials.gov, Study NCT03014297.  (see also ‘added 23 Dec 2016’ below)

added 23 Jan 2017

Mateon Therapeutics, a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, today announced the presentation of final data from Study OX4218 in patients with neuroendocrine tumors (NETs) at a poster session at the ASCO Gastrointestinal Cancers Symposium being held today in San Francisco (20 Jan 17).

Study OX4218 was a multi-center, open label, phase 2 clinical trial to investigate the safety and activity of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid (PNETs or GI-NETs) with elevated biomarkers. Following patients’ completion of Study OX4218, patients were eligible to enroll in Study OX4219, a long-term extension study, if they achieved a biomarker or symptom response. In OX4218 patients were treated with CA4P 60 mg/m2 on Days 1, 8, and 15 of a 21-day cycle for 3 cycles, and in OX4219 patients received CA4P maintenance on Day 1 of a 21-day cycle until disease progression or up to one year.

A total of 18 patients were enrolled in OX4218. One patient (6%) experienced significant symptomatic improvement as measured by ECOG Status and had a partial response per investigator-assessed RECIST and an additional 7 patients (39%) had stable disease. In addition, a majority of patients (53%) experienced an improvement in patient-reported quality of life.  A statistically significant mean change in biomarkers from baseline, the primary endpoint of the study, was not achieved in OX4218 due to the small sample size along with a high intra- and inter-patient variability observed in the biomarkers. A total of 7 patients were enrolled in OX4219, of which 5 patients (71%) had stable disease, including one that continued for 14 months. The partial response and stable disease analyses, as well as other measures from the trial, suggest that CA4P monotherapy has activity in this indication.

“The results of OX4218 and OX4219 confirm that CA4P monotherapy has efficacy in the indications studied, as we have seen with the investigational drug in a number of other monotherapy trials,” said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. “However, we believe that the efficacy of CA4P only becomes compelling when it is used in combination with an anti-angiogenic agent, due to the complementary mechanisms of action for the two agents. Based on the evidence of efficacy observed in this trial, plus an understanding of the benefits of combination therapy, a lead investigator in this trial is sponsoring a 20 patient study in NETs using CA4P in combination with everolimus (AFINITOR®, marketed by Novartis), an anti-angiogenic agent which is already approved and commonly used in this indication.”

Overall CA4P monotherapy was well tolerated. Treatment related adverse events were reported in 77% of subjects. The most common Grade 3-5 AEs (>10%) included: anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases. One Grade 5 adverse event, carcinoid syndrome, was reported and attributed to the underlying disease.

added 23 Dec 2016

There is news of a trial involving this drug which I first published in Jan 2016.  The trial is based at Markey Cancer Centre and is led by Dr Lowell Anthony.  The trial’s primary objective is to establish the maximum tolerated dose of the combination of Everolimus (Afinitor) plus Fosbretabulin in Neuroendocrine Tumors (Grades 1-3) who have progressed after at least one prior regimen for metastatic disease. Read more here.

The original blog published on 10 Jan 2016 follows:

It’s always nice to hear that another treatment for Neuroendocrine Cancer is in the pipeline.  This drug is in the news because it has just been granted designated orphan drug status by the FDA in the US for the treatment of Neuroendocrine Tumours.

My initial thoughts are that it looks promising but it’s very early days.The new drug is formally known as Fosbretabulin Tromethamine or just Fosbretabulin.It also goes by the name of Combretastatin or CA4P which translates to Combretastatin A4-phosphate.In the most basic of terms, it’s a type of vascular disrupting agent (VDA) (note – it’s not chemotherapy).

It appears to be something currently targeted at patients with Advanced Pancreatic or GI Neuroendocrine Tumours with elevated biomarkers.  This is not a new drug and has been around for some years. According to Cancer Research UK, it has already been used for advanced and recurrent ovarian and thyroid cancers.

So how does it work?  The drug makes the cells that line the smallest blood vessels (capillaries) swell up and this has the effect of blocking the blood flow to a tumour. All tumours need a blood supply so that they can get the oxygen and food they need to survive and Neuroendocrine Tumours can be highly vascular. It follows that if the blood flow to a tumour is blocked, there is a chance that it could stop growing or at best kill the tumour (necrosis).  Sounds like the same principles used in Liver Embolization except that this drug has a greater anatomical reach plus a vastly different delivery mechanism via a 10 minute IV infusion.

So why is it a targeted treatment?  The drug will only affect blood vessels that supply cancer cells. Cells lining normal blood vessels contain a protein called actin and this protects the blood vessels from the drug’s effects. Cells lining blood vessels that supply a cancer don’t have actin.

Does it work alongside other treatments?  Interestingly, it appears to be a recommendation to use the drug in combination with anti-angiogenic drugs (i.e. those that can stop the growth of new blood vessels rather than block the blood supply).  Also, according to the manufacturer Mateon, Fosbretabulin has demonstrated broad potential therapeutic value when combined with mainstay oncology modes of treatment including chemotherapy, radiation therapy and the more recent ‘molecularly-targeted therapies’.  In fact if you read the trial addition above dated 23 Dec 16, you will see it’s being tested alongside Everolimus (Afinitor).

So when can we expect to see this drug?  Phase 2 trials were completed at the end of 2016 (results above).  I guess it would still be some years ahead if they wish to proceed. You can see the trial information by clicking here.

I’ll keep this blog live adding to it when I find new or updated information.

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

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PRRT and the NHS England Cancer Drugs Fund

cost cutting vs life cutting?
cost cutting vs life cutting?

As of 4 Nov 15, PRRT was delisted from the NHS England Cancer Drugs Fund. Appeals were made but were rejected, despite the glowing results from the NETTER-1 trial.  Although a replacement system is now in place, PRRT remains barred from routine NHS use.

Please see the following post for the very latest on PRRT worldwide – CLICK HERE

I was extremely disappointed to learn of the decision to remove PRRT (Lutetium or Yttrium) from the Cancer Drugs Fund (CDF) as reported by the NET Patient Foundation. You can read the detail of the decision here: CDF Statement.  PRRT has regularly been described by NET specialists and patients as the “magic bullet” due to its potential to shrink or kill tumours.

This is the second Neuroendocrine Cancer treatment to be withdrawn this year, after the earlier decision on Everolimus (Afinitor) in April . In fact, the recent cuts to the CDF were described in the media as a “massacre” as the list was reduced by two-thirds.  You can see the current CDF list by clicking here.

The timing of these cuts is extraordinary and when you look at the output from recent trial reports presented at the Europetwo-thirdsCongress (ECC) for both Neuroendocrine Cancer related drugs recently cut:

Everolimus

The RADIANT-4 trial said that Everolimus had a significant effect in non-functional NETs which are very difficult to treat.  This is particularly important for Lung NETs as no treatment currently exists.  The RADIANT-2 trial had already proven the efficacy of the drug for advanced carcinoid (in conjunction with Octreotide) and the RADIANT-3 trial proved good data for treatment with advanced functional pNETs.  Read the report here.

PRRT – 177Lu-DOTATATE

The ECC also reported a significant finding from the NETTER-1 trial.  Treatment with the novel peptide receptor radionuclide therapy (PRRT) Lutathera significantly increased progression-free survival (PFS) over Octreotide LAR (Sandostatin) in patients with advanced midgut NETs.  It shows a PFS that has never been shown before in this type of cancer adding that this was significant because these patients have a real unmet medical need.

Lutathera is a 177Lu-DOTATATE PRRT that targets somatostatin receptors, which are overexpressed in about 80% of NETs, to deliver cytotoxic radiation directly to the tumor – See more by clicking here.

To fully understand the background to the problem, you need to understand both PRRT and the Cancer Drugs Fund and a quick primer on both follows.

What is PRRT?

For those who are not entirely sure what PRRT is, here’s a quick primer from The Society of Nuclear Medicine and Molecular Imaging:

Peptide receptor radionuclide therapy (PRRT) is a molecular therapy (also called radioisotope therapy) used to treat a specific type of cancer called neuroendocrine carcinoma or NETs (neuroendocrine tumors). PRRT is also currently being investigated as a treatment for prostate and pancreatic tumors.

In PRRT, a cell-targeting protein (or peptide) called octreotide is combined with a small amount of radioactive material, or radionuclide, creating a special type of radiopharmaceutical called a radiopeptide. When injected into the patient’s bloodstream, this radiopeptide travels to and binds to neuroendocrine tumor cells, delivering a high dose of radiation to the cancer.

The cells in most neuroendocrine tumors have an abundance (called an overexpression) of a specific type of surface receptor—a protein that extends from the cell’s surface—that binds to a hormone in the body called somatostatin. Octreotide is a laboratory-made version of this hormone that binds to somatostatin receptors on neuroendocrine tumors. In PRRT, octreotide is combined with a therapeutic dose of the radionuclides. Yttrium 90 (Y-90) and Lutetium 177 (Lu-177) are the most commonly used radionuclides.  

What conditions are treated with PRRT?

PRRT may be used to treat NETs, including carcinoids, islet cell carcinoma of the pancreas, small cell carcinoma of the lung, pheochromocytoma (a rare tumor that forms in the adrenal glands), gastro-enteropancreatic (stomach, intestines and pancreas) neuroendocrine tumors, and rare thyroid cancers that are unresponsive to treatment with radioiodine.

PRRT is an option for patients:
• who have advanced and/or progressive neuroendocrine tumours
• who are not candidates for surgery
• whose symptoms do not respond to other medical therapies.

The main goals of PRRT are to provide symptom relief, to stop or slow tumor progression and to improve overall survival.

These video’s on Nuclear Medicine are by Professor Val Lewington – the UK’s most experienced person on PRRT.  I was at this presentation and she is absolutely amazing. It’s slightly dated but still very current.  This presentation also covers Octreotide and Gallium 68 scans under the heading of Nuclear Medicine – if you are still unsure about PRRT or Nuclear Medicine in general, these videos are definitely worth a watch.

The Role of Nuclear Medicine in NETs

Q&A Sessions

This is also a great source of information maintained by NET Patients in the USA.  Click here

What was the Cancer Drugs Fund?

The Cancer Drugs Fund was money the UK Government has set aside to pay for cancer drugs that haven’t been approved by the National Institute for Health and Care Excellence (NICE) and aren’t available within the NHS in England. This may be because the drugs haven’t been looked at yet. Or it may be because NICE have said that they don’t work well enough or are not cost-effective. This was introduced as a ‘political statement’ by the then Conservative/Liberal Democrat coalition government in 2010/11.  The aim of the fund is to make it easier for people to get as much treatment as possible.

The Cancer Drugs Fund was for people who live in England. The governments of Scotland, Wales and Northern Ireland decide on how they spend money on health and so far haven’t decided to have a similar programme.

Worth noting that on 1 April 2013, NHS England took on responsibility for the operational management of the Cancer Drugs Fund (CDF). The NHS spends approximately £1.3 billion annually on the provision of cancer drugs within routine commissioning. The CDF was established as an additional funding source to this.

There was a national list of drugs available through the fund – you may have heard this called the priority list. If you met the conditions for a drug that was on the list, you should have been able to have it on the NHS if you live in England. The Fund would also have considered applications on behalf of individual patients for other drugs that are not on the list.  However, under the new system, Individual funding requests (IFRs) relating to cancer drugs will no longer be considered via the CDF process.  All IFRs relating to cancer drugs will now be considered using NHS England’s single, national IFR system, which was updated in January 2016.

The new system came info force on 29 July 2016 and you can read more if you click this link

Summary

Although the decision is shocking to most, it was not totally unexpected as the Government and NHS have been hinting for sometime that the costs of the fund need to be reined in.  In any case if was only ever a temporary arrangement until a another model could be put into place.  There is a political element as the fund was set up by David Cameron with healthcare experts suggesting that it made no sense as a response to rising drug prices.  Moreover, by topping up the fund, the same experts claimed this was making the manufacturers the real beneficiaries of the fund as they have been able to sell their drugs to the NHS at prices that are unaffordable (and therefore unsustainable) for the NHS.

UK NET patients who have advanced and/or progressive neuroendocrine tumours which cannot be removed by surgery and whose symptoms do not respond to other medical therapies, still need help.

Ironically, the UK seems to be intent on cutting provision of the treatment (at least for NHS patients) as the US is trying very hard to formally introduce it.  This is a disgraceful situation and advanced Neuroendocrine Cancer patients and those who may need this treatment in the future are being terribly let down.

I will keep this blog ‘live’ in order to add information as things progress.

Thanks for reading

Ronny
Disclaimer
My Diagnosis and Treatment History

Chemotherapy for Neuroendocrine Cancer


Chemotherapy and Neuroendocrine Cancer

One of the unusual aspects of Neuroendocrine Cancer is that chemotherapy is not normally considered as a ‘standard’ treatment unlike many other cancers. One exception is high grade (Grade 3) where it is often a first and/or second line therapy.  Poorly differentiated Neuroendocrine disease is normally labelled as Neuroendocrine Carcinoma (NEC) but worth pointing out there is now a Grade 3 well differentiated classification known as a ‘Grade 3 NET’ rather than Grade 3 NEC. Depending on Ki67 score, there could be differing treatment options for Grade 3 NET and Grade 3 NEC.  Read more in my articles Staging and Grading and High Grade.

Many people think Chemotherapy has a short life span due to recent advances in medical science, some citing Immunotherapy as it’s replacement. However, it’s far too early to write off chemotherapy which is still used in many scenarios and remains a tool in the arsenal of cancer treatments and is predicted to do for some time yet.  See more informed reporting about this below.

Which Chemo for which Neuroendocrine Cancer type and grade/differentiation? 

The type of chemo or the combination of different treatments will often depend on the tumour type and anatomical location involved but may include (but not limited to): Capecitabine (Xeloda), Temozolomide (Temodal), Fluorouracil (5-FU), Oxaliplatin (Eloxatin) Cisplatin, Etoposide (Etopophos, Vepesid), Carboplatin, Streptozotocin (Zanosar). Some of these may be given as a combination treatment, e.g. CAPecitabine and TEMozolomide (CAPTEM). many as a combo treatment.  There is a useful article explaining the role of Ki-67 in determining optimal chemotherapy in high grade neuroendocrine tumors.

Cytotoxic chemotherapy is often inadequate for treatment of Grade 1 and 2 (well differentiated) Neuroendocrine tumours which have a low proliferation index. Chemotherapy does not appear to like their slow cytokinetic growth. However,  it tends to work better on certain parts of the anatomy than others, e.g. pancreatic NETs and Lung NETs.  Of interest is a statistic from NET Research Foundation indicating that 23% of patients who were to be prescribed chemo had their treatment changed to a non-chemo option following a Ga68 PET scan.  Read more here.

For second line therapy (including for well differentiated NETs where other conventional treatments are not working), chemo may be given.  These include (but not limited to) Capecitabine, Temozolomide, Bevacizumab, Xelox, Folfox.  There are other specialist chemos for Mixed Neuroendocrine Non-Neuroendocrine Neoplasms (MiNEN).

‘Horses for Courses’ – Chemo is sometimes used for well differentiated lower grade NETs.

There’s a myth that circulates the NET patient forums along the lines of “chemotherapy does not work for NETs“.  That’s not entirely true but most will not get chemotherapy and this can often lead to confusion in those with Stage 4 cancer when asked by others why they are not receiving chemo.

Capecitabine plus Temozolomide (CAPTEM for short) is fast becoming the standarad chemotherapy treatment when it is required with certain lower grade NETs.  Dr Robert Fine says the results of the CAPTEM trial showed “tremendous responses in every neuroendocrine tumor”. The treatment elicited a response rate of 45% and a stable disease rate of 52% including those with certain types of NETs and pituitary tumours – types of neuroendocrine tumour that are notoriously ‘chemoresistant’.  You can read more about this here (click here) and you can also listen to Dr Fine talking about this on a short You Tube video clip – (click here).  Clearly it’s true that it’s not going to work for all.

Other CAPTEM Resources:

  • There’s a very interesting report on the use of CAPTEM in NETs – (click here)
  • CAPTEM Trial Document – (click here)

PRRT and Chemo Combo Treatment

In Australia, they’re also using a combo treatment of chemo (CAPTEM) and PRRT – I blogged about this click here.

“Chinese Dumplings”

There’s also a useful surgical technique which includes the use of intra-operative chemo, known as “Chinese Dumplings” – I wrote about this click here.

Chemo Embolisation

My Oncologist did mention Chemotherapy on my initial meeting, that was a shock and realisation I had something serious.  However, that never transpired but I was once scheduled to have a chemo-embolisation (or TACE, Trans-arterial Chemo Embolisation). Clearly TACE is more targeted than conventional and generally systemic chemotherapy techniques. Perhaps that my Oncologist actually meant.  The chemo-embolisation never transpired either (long story).

Chemotherapy vs Targeted Biological Agents and Somatostatin Analogues

I often see people describing Somatostatin Analogues (Lanreotide/Octreotide), Afinitor (Everolimus) and Sutent (Sunitinib) as chemo but that’s isn’t technically correct, and I’ve yet to find a NET Specialist or a NET Specialist Organisation who classifies these drugs as chemo.  See my article “Chemo or not Chemo” (click here).

Future of Chemo?

A lot is written about how much longer chemo will be around.  It gets a bad press – I suspect mainly due to the side effects.  There are suggestions that it will eventually be replaced by Immunotherapy and other treatments downstream.  However, immunotherapy is really still in its infancy and there remains a lack of long term data on success rates and side effects.  I suspect chemo will be around for a while longer, particularly for cancers where it has a track record of curing according to ASCO.  Very recently (June 2018), cancer experts said that chemo will be around for a long time yet – read more here

None of the content of this post should be interpreted as advice or a  recommendation for chemotherapy. If in doubt about suitability for any form of chemo, or the type you have been prescribed, patients should seek the advice of their treating doctor or NET specialist.

Thanks for reading

Ronny

I’m also active on Facebook.  Like my page for even more news.  I’m also building up this site here: Ronny Allan

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients included
Please Share this post for Neuroendocrine Cancer awareness and to help another patient