LUTATHERA (PRRT) – NETTER 2 Clinical Trial for Grade 2/Grade 3 Neuroendocrine Neoplasms


netter 2

Brief Summary

The NETTER-1 trials led to the approval of Lu177 (or Lutathera), more commonly known in the community as Peptide Receptor Radio Therapy (PRRT).  This led to an explosion of availability across the world but many gaps in service remain.

Many PRRT spin off trials are in the pipeline looking at different types of PRRT, mainly using slightly different radionuclides and techniques.  However, NETTER-2 builds on the success of the approved version formally known as Lutathera.

The aim of NETTER-2 is to determine if Lutathera in combination with long-acting octreotide prolongs PFS in GEP-NET patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naïve patients are eligible, as well as patients previously treated with SSAs in the absence of progression. This is a phase 3 trial that will be hoping for 222 participants at multiple locations.

This is an exciting trial because there are already data produced indicating that PRRT can be used on high grade tumours providing they have sufficient and efficient somatostatin receptors and a Ki67 of less than 55%.  2019 Updated data for Grade 3 Neuroendocrine Neoplasms: “Compared to studies evaluating the efficacy of chemotherapy for NEN patients with a Ki-67 index less than or equal to 55 percent, PRRT has a longer overall survival rate–22 months versus 14 months,” the researchers pointed out. “These results suggest that PRRT, rather than chemotherapy, may be a superior first-line therapeutic option in selected patients with a high level of SSTR expression and a Ki-67 index of less than or equal to 55%.”  Read more here.

This article will be fleshed out in due course. No locations listed yet.  Not recruiting yet.  Criteria listed – important section if this trial interests you. Clinical Trials document here.

In the meantime, read more about Lutathera (PRRT) by clicking here.

This looks like a very exciting development.

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!

Ronny Allan is an award winning patient leader and advocate for Neuroendocrine Cancer.


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Round up of NANETS 2017 – Let’s talk about NETs #NANETS2017

NANETS (North American Neuroendocrine Tumor Society) is one of the biggest NET conferences, bringing together NET Specialists from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field of Neuroendocrine Neoplasms (Tumors and Carcinomas). This is fairly complex stuff but much of it will be familiar to many. I’ve filtered out several outputs from the conference which I think are both relevant and topical to patients. The list is below allowing you to easily peruse and read further via linkages if you need to read more.  Remember, some of these are extracts so do not contain all the details of the research or study – although some of the linkages will take you to in-depth information if that’s your bag. Where applicable, I’ve also linked to some of my blog posts to add context and detail in patient speak. The list comprises articles which were published in medical news media and for which I received alerts.  It does not comprise the entire schedule of NANETS 2017. I may add more to the list if other relevant and interesting articles are published downstream.

Please note:
Some of the output from the conference is in ‘study form’ and has not yet been published as peer-reviewed data (important notice to readers).

NANETS to Bring All Specialties in the NETs Community Together for 10th Annual Symposium

Interview with Michael Soulen MD.  Nice introduction.

https://goo.gl/tMT6KS
Location of Neuroendocrine Tumors in the Small Bowel Does Not Affect Survival

 

https://goo.gl/zf9k9j
Diagnosing and Treating NET-Related Diarrhea

 

Incorporated into my Diarrhea article – https://goo.gl/PwsXmX
Emerging Therapies, Biologic Discoveries, and Improved QoL on Horizon for NETs

 

https://goo.gl/p4cCyd
Retrospective Database Analysis Studies Somatostatin Analog Usage in NETs

 

https://goo.gl/KWM4p7
Regional Lymph Node Involvement and Outcomes in Appendiceal Neuroendocrine Tumors: A SEER Database Analysis. https://goo.gl/vfF4DA
Personalizing Therapy With PRRT and Improving Imaging With SSTR-PET Brings Novel Options to NETs Landscape

(new term SSTR-PET generically meaning any PET scan using somatostatin receptors), e.g. Ga68 etc.

https://goo.gl/s8sked
PFS and OS After Salvage Peptide Receptor Radionuclide Therapy (PRRT) with 177-Lu[Dota⁰,Tyr³] octreotate in Patients with GastroEnteroPancreatic or Bronchial NeuroEndocrine Tumours (GEP-NETs) – The Rotterdam Cohort https://goo.gl/yZ56YZ
Molecular Classification of Neuroendocrine Tumors: Clinical Experience with the 92-gene Assay in >24,000 Cases https://goo.gl/aqgfRf
Neuroendocrine Tumors: A Patient Survey

“Regarding their biggest challenges, patients reported fatigue as their biggest challenge followed by diarrhea, sleep disturbances, and pain.”

https://goo.gl/qEeNRM
Phase III Trial Needed to Confirm Clinical Benefit of Cabozantinib in NETs

 

Incorporated into my Cabozantinib article – https://goo.gl/mR2yFT
QOL Improvements in NETTER-1 Phase III Trial in Patients with Progressive Midgut Neuroendocrine Tumors. (I think this is well-known but no harm in repeating it!) https://goo.gl/UmKsFi

 

The full link to all poster abstracts for NANETS 2017 can be found here

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!

Theranostics for Neuroendocrine Cancer – A Find and Destroy Mission

theranostics
Courtesy of Pashtoon Kasi MD on Twitter https://twitter.com/pashtoonkasi/status/1078675398601396224

Theranostics is a joining of the words therapeutics and diagnostics. You may also see it conveyed as ‘Theragnostics’ and these terms are interchangeable. The basic aim of theranotistics is to find and then destroy the ‘bad guys‘. With Neuroendocrine Cancer, finding the tumours (the bad guys) can often be a challenge – they can be small and/or difficult to find – they are sometimes expert at camouflage. Moreover, once found, they can then be difficult to treat (destroy), as they can often prove resistant to conventional cancer drugs and many are inoperable due to sheer quantity, spread and positioning. When they are found and identified, it’s also really helpful to know from the intelligence gathered, how successful the destroy (therapeutic) part of the mission might be.

The nuclear scan uses the same targetin agent as the therapy, therefore if you cancer lights up on the nuclear scan, then the therapy will find its way to the cancer and hopefully work well. That is the beauty of theranostic pairing, i.e. the use of the same agent in the diagnostics – the ability to find, estimate likely success criteria and then hopefully destroy – or at least reduce the capability of the tumours and extend life.

A great example of an approved Theranostic Pair in Neuroendocrine Cancer, is the combination of the Somatostatin Receptor based Ga68 PET scan using NETSPOT or SomaKit TOC™ (US/Europe respectively) and Peptide Receptor Radiotherapy (PRRT) using Lutathera which both target NETs expressing the same somatostatin receptor, with PRRT intended to kill tumor cells by emitting a different kind of low-energy, short-range radiation than that of the diagnostic version. As mentioned above, the Ga68 PET scan can give a reasonably indication of therapeutic success using PRRT based on measurements taken during the scan (too complex for this article).

Theranostics – a step towards personalised medicine – graphic courtesy of Advanced Accelerator Applications.

THERANOSTICS – FIND

Octreoscan vs Ga68 PET

Ga68 PET

Newer imaging agents targeting somatostatin receptors (SSTR) labelled with 68 Ga have been developed, namely, DOTATATE, DOTATOC and DOTANOC. They are collectively referred to as SSTR PET.

The full titles of the 3 types are:

68Ga-DOTA-Phe1-Tyr3-Octreotide (TOC),
68Ga-DOTA-NaI3-Octreotide (NOC),
68Ga-DOTA-Tyr3-Octreotate (TATE).

The main difference among these three tracers (DOTA-TOC, DOTA-NOC, and DOTA-TATE) is their variable affinity to SSTR subtypes. All of them can bind to SSTR2 and SSTR5, while only DOTA-NOC shows good affinity for SSTR3.

These agents have several benefits over In111-pentetreotide (Octreotide scan), including improved detection sensitivity, improved patient convenience due to the 2 hour length of the study (compared to 2 or 3 days with Octreoscan), decreased radiation dose, decreased biliary excretion due to earlier imaging after radiotracer administration, and the ability to quantify uptake. The quantification of the uptake can help decide whether a patient is suitable for PRRT. Eventually, all Octreotide scans should be replaced with SSTR PET. To confirm the advantages of SSTR PET over Octreotide scans, a study comprising 1,561 patients reported a change in tumour management occurred in over a third of patients after SSTR PET/CT even when performed after an Octreotide scan. Worth pointing out that SSTR PET is replacing the ageing Octreotide scan and not conventional imaging (CI). You can see the recommended scenarios for use of SSTR PET in this article published by the Journal of Nuclear Medicine

Ga68 PET scans have been in many locations for some time. Current excitement is focused on USA locations with Ga68 PET (NETSPOT) only recently approved (DOTATATE). Other countries/scan centres may use one of the other types of imaging agent.

Read much more about this scan in my detailed article on Ga68 PET here.

So SSTR PETs above have the ability to find and estimate likely success criteria for therapy. We are now in a position to move on to ‘THERApy’ – e.g. Peptide Receptor Radiotherapy or PRRT.

THERANOSTICS – DESTROY

click on picture to watch video

Lutathera® (note the ‘THERA’ which makes up the brand name)

Definitions:

Europe Approval: LUTATHERA®(lutetium (177Lu) Oxodotreotide) is indicated for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEPNETs) in adults.

USA Approval: LUTATHERA® (lutetium Lu 177 dotatate) is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults.

For commercial purposes, the drug may be slightly different on a regional basis. For all intents and purposes it does the same job.

As an example of how the drug is administered, please watch this short video from the European site:

Video courtesy of Advanced Accelerator Applications
Please see the following post for a summary of PRRT activity worldwide. Please note this linked article is not designed to contain a list of every single location or country available – please bear that in mind when you read it – CLICK HERE

I’m very grateful to the team at Advanced Accelerator Applications (a Novartis Company) for allowing me to use their site for graphics and videos.

In another ‘theranostic’ development, check out my article on the Satoreotide trial (Ops 201/202) from Ipsen (of Lanreotide fame) – click here to read – the trial is recruiting.

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

Read my Cure Magazine contributions

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

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