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

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"Interestingly, the ORR in pancreatic NETs was 44%, a rate not seen before with targeted agents,"

Jonathan Strosberg, MD, head of the neuroendocrine tumor division at Moffitt Cancer Center in Tampa Tweet

Lenvatinib has 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 is 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. Click here
  • 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. Click here
  • 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.

In this multicenter, open-label study involving 111 patients, treatment with lenvatinib (Lenvima) led to an overall response rate (ORR) of 29.9%, with a particularly high ORR — 44.2% — in patients with pancreatic NETs, reported Jaume Capdevila, MD, PhD, of Vall Hebron University Hospital in Barcelona, and colleagues.

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

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.

ASCO Extract 2019

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.

Other clinical trials

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

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

Clinical Trial using Lenvatinib and Keytruda in Treating Patients With Advanced, Unresectable Neuroendocrine Tumors

ClinicalTrials.gov Identifier: NCT03290079.  a trial run by Moffatt Tampa.  As of 3rd Aug 2022, the recruiting is suspended pending interim results analysis.

Clinical Trial for Pheo/Para

ClinicalTrials.gov Identifier: NCT03950609.  Based out of May Rochester.

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. TALENT Clinical Trials Document NCT02678780 – click here

5. Manufacturer’s 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 the document for contact details, quite often these documents can be behind in updating. Trial start date is recorded as 30 June 2019.

7.  ClinicalTrials.gov Identifier: NCT03950609. For Pheo/Para.

8. ClinicalTrials.gov Identifier: NCT03290079. Lenvatinib with Keytruda

9.  ASCO Journal of Clinical Oncology DOI: 10.1200/JCO.20.03368 Journal of Clinical Oncology published online May 04, 2021.

General Clinical Trials Disclaimer

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 in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. 

Inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan. 

 
 

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3 thoughts on “Clinical Trial: Lenvatinib Efficacy in Metastatic Neuroendocrine Tumors (TALENT)

  • Liz

    Hi, there. This is straight from the horse’s mouth: I was part of the Spain Lenvatinib trial from May 2016 to end of October 2017 (I live in Madrid). Having been diagnosed with and had surgery for locally advanced pancreatic neuroendocrince cancer in 2011, I experienced PFS till late 2015 when the beast came back in the form of liver metastasis. A first clinical trial did not work and I entered the Lenvatinib trial. I was put on the full 24 mg dose initially but this was gradually reduced and I was on the minimum 10mg by the time I exited the trial in 2017. I left as my tolerance to the toxicity had reached its limit and I could not continue with the nausea, diarrea, severe joint and muscular pain. I should add that I am very sensitive to medication. Over the 18 months I was on the trial, the cancer spots on my liver shrank considerably and my CgA levels are today almost within normal range. (I take PPIs which can skew results). I was also treated with SBRT. Since then, I have been put on Somatuline Autogel 120 and I have 3-monthly CT scans, with an Octreoscan SPECT/CT scan before Christmas. Nearly 15 months after coming off Lenvatinib I show no tumoral activity. Needless to say, I hold my breath between scans (next one in March) but know that awareness of neuroendocrine cancer has grown enormously since my initial diagnosis – thanks in part to blogs such as Ronny’s – and that this impacts research. Sad deaths such as Aretha Franklin’s also help to strengthen awareness. My oncologist tells me that should I have a relapse, then he’ll recommend PRRT. I am blessed to live in a part of the world where all this is a) available and b) available through the public health system.

    Good luck to one and all and unending thanks to Ronny for keeping us up to date.

  • Margaret Winter

    There is so much hope now in this sneaky cancer . I just want to live and live …life is so wonderful…now there is even more hope and time for us n e t s people!! Just a shame sometimes we have to shout out for it! My doctor recently scared me by calling after a 5 1ahh sample saying it was high again…I immediately brought my consultant appointment forward and worried constantly for the weeks wait….only to be told it was actually LOWER than ever before and I can now after 2 and a bit years go to 6 monthly appoint….jumping for joy was an understatement!!!

  • jean borden

    Keep it up Ronnie….you are doing a great job in reporting the latest and greatest. Liver Mets continues as the most irritating but treatable in different stages. We need more and more on this topic! Thank You!

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