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There’s a lot of Immunotherapy stuff out there! However, I also wanted to break it down and perhaps see if I can pick up the what, when, why, where and how in regards to Neuroendocrine Cancer. It’s really difficult, not least because the picture is not clear and there is no general roadmap printed, let alone one for Neuroendocrine disease. Immunotherapy for NETs was discussed at ENETS 2017 in Barcelona. The presentation that sticks out was one given by Dr Matthew Kulke, a well-known NET Specialist in Dana Ferber Boston. My reaction to the presentation was one of ‘expectation management’ and caution i.e. it’s too soon to know if we will get any success and when we will get it. He also hinted that it’s more likely that any success will first be seen in poorly differentiated high-grade Neuroendocrine Carcinoma (NEC). Dr Jonathan Strosberg also said similar in a post here. In fact, from below you will see that grade 3 poorly differentiated is where the bulk of trial activity is (…..but read on, there is some action around plain old well differentiated NETs).
Let’s start with Pembrolizumab (Keytruda)?
‘Pembrolizumab’ better is more famously known as ‘Keytruda‘. This drug crops up everywhere and it has connections to many different cancers. Before I talk about this trial called PLANET, it’s very useful to take a quick look at the history of Keytruda which was only really made famous after former US President Jimmy Carter was treated with it for metastatic melanoma. There was a lot of media hype surrounding what made his treatment successful as he was also given radiation for his brain tumours and his large liver tumour was removed by surgery. However, putting the hype and conjecture to one side, Keytruda’s CV is pretty impressive:
Pembrolizumab (Keytruda) is currently approved to treat:
- Hodgkin lymphoma in adults and children. It is used in patients whose disease is refractory (does not respond to treatment) or has relapsed after at least three other types of treatment.
- Melanoma that cannot be removed by surgery or that has metastasized (spread to other parts of the body).
- Non-small cell lung cancer that has metastasized. It is used:
- With pemetrexed and carboplatin as first-line treatment in patients with nonsquamous disease.
- As first-line treatment in patients whose cancer has the PD-L1 protein and does not have a mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene.
- In patients whose cancer has the PD-L1 protein and got worse during or after treatment with platinum chemotherapy. Patients whose cancer has EGFR or ALK gene mutations should receive Pembrolizumab only if their disease got worse after treatment with an FDA-approved therapy for these mutations.
- Squamous cell carcinoma of the head and neck that has metastasized or recurred (come back) in patients whose disease got worse during or after treatment with platinum chemotherapy.
- Urothelial carcinoma (a type of bladder cancer) that is locally advanced or has metastasized. It is used in patients who cannot be treated with cisplatin or whose disease got worse during or after platinum chemotherapy.
- Microsatellite instability-high (MSI-H) cancer that is metastatic and cannot be removed by surgery. It is used in adults and children for:
- Solid tumors that have gotten worse after other treatment or that cannot be treated with other therapies.
- Colorectal cancer that has gotten worse after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
MSI-H cancer has certain genetic mutations and may not respond to some types of treatment.
The most recent approval in May 2017 MSI-H disease is a very interesting development as it’s the US FDA’s very first approval on a tissue/site agnostic basis. You can read about this approval here. Cancers of the breast, prostate, thyroid, bladder, colon, rectum and endometrium are just some of the cancers that have been found to have these biomarkers and would be new possible targets for Keytruda. There’s a great article which explains this approval in an easy way – click here to read.
Other approvals are anticipated.
So what about Neuroendocrine Neoplasms?
I found the following trials for high-grade NEC:
- currently recruiting Pembrolizumab (Keytruda) for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma (Pembro NEC)
- currently recruiting A Study of Pembrolizumab (Keytruda) in Patients With Neuroendocrine Tumors
- currently recruiting Pembrolizumab (Keytruda) – based Therapy in Previously Treated High Grade Neuroendocrine Carcinomas
- This trial is interesting. Nivolumab (Opdiva) and Ipilimumab (Yervoy) in Treating Patients With Rare Tumors It’s a multiple cancer setup and includes several of the less common NET/NEC types including ‘Lung Carcinoid’, ‘Anal NEC’, ‘Gastic NEC’, ‘Pancreatic NEC’ ‘Esophageal NEC. Interesting because this is the drug combo that NEC patient Danielle Tindle has moved onto after Keytruda didn’t really work in the medium to long-term (see the Danielle Tindle story below). Looking at the list in the trial document, I’m thinking they might mean high-grade Lung Neuroendocrine rather than ‘carcinoid’. I could be wrong. It’s currently recruiting.
- I also have some evidence of the use of Pembrolizumab (Keytruda) by an Australian high-grade thymus patient – I posted something here (Danielle Tindle)
- Merkel Cell Carcinoma – a type of Neuroendocrine skin carcinoma is benefiting from Immunotherapy – check out this summary from OncLive by clicking here. Worth noting that this type of Neuroendocrine Carcinoma already has an FDA approved immunotherapy drug (Avelumab (Bavencio)) with another pending (Keytruda)
Please also see the wonderful work done by NET Research Foundation who are using their funds to explore the use of Immunotherapy in NETs – check out their update by clicking here.
But what about just plain old well differentiated low or moderate grade NETs?
I found the following:
Pembrolizumab (Keytruda) in combination with Lanreotide
According to the trial documentation, it’s for patients with non-resectable, recurrent, or metastatic well or moderately (sic) differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). i.e. most of us. It is recruiting. You can read about the PLANET trial by clicking here. Make sure you fully check the inclusion and exclusion criteria. Please note the incorrect reference to ‘moderately differentiated’ – this is no longer used in the grading classification for Neuroendocrine Neoplasms.
Study of Pembrolizumab in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28) – NCT03054806
You can read an update of progress by clicking here. This study will assess the efficacy and safety of Pembrolizumab (Keytruda) administered to participants with incurable advanced biomarker-positive solid tumors that have not responded to current therapy or for which current therapy is not appropriate. This study may be a overarching document for a number of sub-trials which will individually recruit. Apologies for the use of the antiquated and misleading term ‘Carcinoid’ within the document.
Study for the Evaluation of Pembrorolizumab (MK-3475) in Patients with Rare Tumors (Experimental: Paraganglioma-Pheochromocytoma Group)
This study is recruiting at MD Andersen Houston Texas. Read more here.
Atezolizumab and Bevacizumab in Solid Tumors
In 2016, US FDA approved Atezolizumab (TECENTRIQ) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). Bevacizumab (also known as AVISTAN) is a well known drug already used to treat many cancers. Avastin is not actually Immunotherapy but is a tumor-starving (anti-angiogenic) therapy, i.e. its purpose is to prevent the growth of new blood vessels …. ergo this is a combo treatment using an Immunotherapy drug and an anti-angiogenic drug.
- Well differentiated Neuroendocrine tumors, Grade 1 or grade 2 according to reviewing pathologist
- Progressive disease over the preceding 12 months
- Any number of prior therapies
- Patients using a somatostatin analogue for symptom control must be on stable doses for 56 days prior to enrolment.
According to the trial documenation, there are two ‘baskets’ of types: Pancreatic NET (pNET) and “extrapancreatic” (i.e. beyond or not in the pancreas) including typical or atypical Lung NETs. Merkel Cell Carcinoma (a type of Neuroendocrine Carcinoma of the skin) is also included in the trial. You can read about this trial by clicking here. Make sure you fully check the inclusion and exclusion criteria. Again, within the trial documentation, please note the incorrect reference to ‘moderately differentiated’ – this is no longer used in the grading classification for Neuroendocrine Neoplasms.
By the way, what exactly does Immunotherapy do?
For those still wondering what cancer immunotherapy actually is, this is the most basic description I could find!
Immunotherapy – Hype or Hope?
I mentioned above that there was a lot of hype surrounding Keytruda and other immunotherapy treatments. You may therefore enjoy this CNN article about the hype and hope aspect, it was given considerable sharing at ASCO17 – read the article by clicking here
If you’re on an Immunotherapy trial not listed here, please let me now so I can update the post. Thanks in advance.
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Ronny Allan’s ‘PoNETry’ © series can be shared with poetry credit to:
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You may also enjoy my Invisible Illness ‘PoNETry’ – click here
Ronny Allan’s ‘PoNETry’ © series can be shared with poetry credit to:
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Before I was diagnosed with cancer, my relationship with my health was fairly distant. I had minor irritants that seemed to come back now and then, nothing that was going to kill me. So I just put up with most of it and time was frequently a good healer. Occasionally, I would use medicine to speed up the healing or ask a doctor for advice. Even leading up to my diagnosis, this was my strategy despite some strange things going on. Luckily for me, the ‘system’ picked up something suspicious and I am where I am today. It’s amazing to think a cancer can grow inside you for years causing a lot of damage but without a grand announcement.
Following diagnosis, I got quite a lot of attention in the first 2 or 3 years as I went through various surgical and other types of treatment, and I eventually earned the accolade of ‘stable’. Not cured, not in remission, not totally free of disease, just ‘stable‘. I guess I’m one of millions of people who now have a condition to live with for the rest of their life.
I may be stable but I still need support and surveillance!
But I haven’t really been left alone, I have meetings with my specialists every 6 months plus routine surveillance testing. I have my GP (PCP) on tap via same day appointments. Thankfully, my tumours are slow growers and the biochemistry results that check their growth and function have been normal for some years now. I also have my specialists’ telephone numbers in the event of an emergency. The other great thing is that I’m lucky to have a direct line to a specialist Neuroendocrine Cancer Nurse for routine stuff. So I can sit back and relax, right? ……… Sounds good but not really the whole story.
I’m in tune with my body
I can honestly say I’ve never been more in tune with my body – there’s nothing like a cancer diagnosis to force you into a change of attitude. Not just about how you look after your body but learning how to read the signs and assess risk. However, the difficult area with this disease is that many of the side effects of treatment can mimic the symptoms of a recurrence or further spread and vice versa. And sometimes there can be no rhyme or rhythm (or logic) when patients experience these things. I once wrote about the “Neuroendocrine Cancer Jigsaw” where patients had pieces called Signs, Symptoms, Side Effects, Secondary Illnesses, Syndromes, Comorbidities and Coincidences. I also include the proverbial ‘missing piece’ as part of the jigsaw! However, I do think the ‘missing piece’ can sometimes be a metaphor for an instantly contactable NET expert or even some experience and education by the patient or a trusted advocate.
Sorting out the symptoms
The comorbidity and coincidence pieces were belated add-ons to the list because sometimes it not all about the cancer – even cancer patients get regular diseases and ailments. The difficulty is working out if there is a connection or not. Take my 2017 issue of back/hip/leg pain for example. I analysed all the timings in my diary (…top tip, keep a diary), there were no common connections to any particular occurrence or activity for all occurrences of the pain. I got some pain killers and decided to tough it out. After 14 days, I got fed up and saw my GP (PCP). I also ran it past my NET Specialist Nurse for assurance. After 22 days, I was still doing pain killers, waiting on a physiotherapy appointment; and doing back exercises at home. Why is my back pain suddenly a lot worse? My Calcium and Vitamin D are checked regularly and everything is in range. I’ve been receiving somatostatin analogues for over 6 years, so that might be a factor. I also reminded myself I’m no longer 21 (so did my NET Nurse!). Three months later, after seeing a physiotherapist, things improved. However, I would be lying if it didn’t cross my mind that the problem could be bone metastasis. I studied the symptoms of bone metastasis and concluded that I have none of those other than the pain. I analysed my recent scan which said there were “no bony lesions”. I also registered the fact that my biochemistry results are rather good and have been for 6 years.
And then there were the 3 episodes of constipation where the possibility of a bowel obstruction floated around in my thoughts. However, time was once again a healer (along with some quick advice from my specialist NET Nurse!).
A couple of years ago, I thought I felt a lump on my right clavicle by the sternum. However, an MRI later dismissed it as nothing. Due to a piece of metal in my body, to be honest I was more scared about the MRI than the potential lump!
I always remember a great quote from Dr Eric Liu “Even NET Patients get regular illnesses“. He’s right. But it’s also right that people living with a long-term cancer can live in perpetual fear of a worsening state of health or a recurrence of the cancer. For the incidents I highlighted above, the fear that these things were related to cancer growth or recurrence did go through my mind.
Fear can actually be a side effect of cancer
I think all those living with cancer need to be alert and be proactive via education and communication with their medical team and GP (PCP). However, stopping yourself thinking that anything wrong with your body is somehow connected to the cancer, perhaps needs a different approach, particularly if you have a higher than average risk for recurrence. Fear of cancer relapse or recurrence, is said to be associated with poor quality of life, greater distress, lack of planning for the future, and greater healthcare utilisation. However, if you do suffer from this type of fear, you’re not alone. A recent study stated that 50 percent of all cancer survivors have moderate to high, or clinically significant, fear of cancer relapse, which could persist over the whole trajectory of their illness. Younger patients might have a bigger challenge on their hands as their future is uncertain. Patients with young children have an additional concern, that’s another fear area and a very difficult and tough one.
Psychological problems – another unmet need? Probably.
Conquering fear is difficult and no one size fits all. However, in the most general terms I would suggest the following 7 tips:
- Accept your diagnosis – you have cancer, it has the potential to change your life, you most likely need to make adjustments. But this is not to say you also accept that improvements cannot be made and things will not get better …. because they can. This is particularly important for those with incurable cancers needing treatment for the foreseeable future. I accepted my situation very early on and I think that has been helpful in the long-term. Prognostic detail is a worrying thought and a difficult one. However, no-one really knows for sure. After 8 years with an incurable metastatic cancer, I’m still here and continue to be heartened by comments such as these here (click here).
- Accept that your road will probably not be straight and smooth. There will be bumps and bends and you will need to deal with them as and when they arise. Don’t try to second guess what the bumps and bends might be and then worry in case they happen. No-one really knows for sure and they might not happen.
- Identify your triggers – what is it that is triggering your thoughts? For me it’s more physical things like the lump, constipation and back pain. Other triggers for some might simply be an anniversary of a diagnosis or a treatment etc (or both), or an upcoming treatment. Think about how you can get past these obstacles. For example, on ‘cancerversaries’, plan to be doing something that’ll take your mind of it. For physical things including upcoming treatment, it’s all about what I said above, education, risk management and communication with your medical team ….. put yourself in control. I also have great sympathy for younger patients and those with young dependent children. I can’t put myself in their shoes and all I can suggest is that these tips are still relevant in some way.
- Talk about it. Family, friends, other patients, your medical team. I don’t’ have any issues talking about it – writing posts in my blog is also really therapeutic for me (even this one!) and I hope others appreciate it too. Patient forums can be frighteningly good (but …. be careful, many can also be good at frightening and stressful). However, try not to become a ‘cybercondriac’ …… although talking to me is still allowed!
- Focus on Wellness. This is a huge area and it’s pretty much up to you to resolve. Yes, some willpower is involved and it includes both physical and mental wellness. For me I try to do exercise when I can (mostly walking) and I try to make sure I get 8 hours sleep (this is a fairly recent tactic which is really helping with fatigue). With diet, I try to avoid anything that greatly exacerbates the side effects of my treatment. Travelling, family and visiting places with fantastic views is most definitely a tonic for me (and that normally means exercise to get there). Anything that makes you relaxed!
- Be patient. Fear of your condition taking a downwards movement will probably never completely go away but perhaps as I said above, time is a healer. It took me over 3 years to become more relaxed about my own future.
- If all the above doesn’t work, perhaps professional counselling is required? There are specialists who work with cancer patients to help them accept that fear of recurrence/relapse is a normal part of the cancer experience. They can help you develop strategies to cope with your fears and move forward with your life.
If you think your fear of recurrence or relapse is unmanageable, I strongly encourage you to talk with your doctor or a counseller.
Remember …….. “Googling your symptoms when you’re ill is the most efficient way to convince yourself you’re dying”. Anon
Stay well all
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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.
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.
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:
- ASCO 2017 – Let’s talk about NETs #ASCO17. Extracts on the NET subjects being discussed at the biggest Oncology conference in the world.
- Waiting on PRRT ….. light at the end of the tunnel? Contains the latest update as at 31 May so this is really hot off the press.
- Neuroendocrine Tumours – not as rare as you think. Now containing the latest SEER data confirming NETs no longer rare in USA.
- NETwork with Ronny © – Newsletter April 2017. ICYMI
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
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.
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
- 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’)
- Twitter – 3915 / 3017 Follow me here @RonnyAllan1 / @NETCancerBlog
- Total Blog Views: 292,626
- Blog with most views: 9211 – The 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!
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Hey, I’m also active on Facebook. Like my page for even more news.