Lenvima/Lenvatinib with & without Everolimus–New FDA approval

Another new drug for those of us with ‘unresectable and advanced” kidney cancer!  YEA or is is just, yea? What does this mean to the patient in this situation as he struggles to get the best treatment possible?

The approval is for Levatinib in combination with Everolimus (Afinitor) for advanced kidney cancer or unresectable (surgery not possible) kidney cancer in patients who have had previous TKI treatment–Sutent, for example.  This was based on a Phase II trial, so a bit unusual in that regard.  Generally the FDA waits until there is a larger Phase III trial, so this reflects the  need for better second-line treatments.

It is always great to have another tool against kidney cancer, and on top of the recent approval of Nivolumab (Opdivo) and Cabozantinib (Cometryx), but do note that all three are for second line use, after the first line meds have failed.  Current first line drugs include high dose interleukin, Sutent and others.

All the patients in this trial had previously used and quit responding to the first line TKIs, and are compared in three arms

Arm 1)  Lenvatinib alone–52 patients—didn’t make the grade

Arm 2) Everolimus alone–51 patients—standard of care for second line

Arm 3) Lenvatinib & Everolimus in combo–51 patients–the new approval.

Not a very big trial, so harder to make broad judgements!

Everolimus is already approved for second line use, and Lenvatinib alone was NOT approved except in combination with Everolimus.  With that, just ignore Arm 1.  The big news is that the combo improved median Progression Free Survival (PFS) in the combo to 14.6 months vs 5.5 months with Everolimus. The median gives us the POINT in time at which half got “progressed” on their disease, ie, the damn stuff grew, while the other half had not yet had progression.  Not an average, so half of the combo patients had PFS by 14.6 months, and the other combo half did not have PFS until after that time.

The median Overall Response Rate (ORR) was not very high–but quite typical–and important to understand.  The combo patients had a 37% ORR, so about 1 in 3 had a measurable response.  That compared to just 6% with everolimus.  The most important measure to patients is median Overall Survival. This is usually measured when one-half of a patient group has died, so there are always patients who live beyond that median point. The combo OS was 25.5months vs the Evero alone OS of 15.4 months.  There was no mention I could find whether there were patients alive at this point, but assume there were. Love to know if there are very long term survivors in the combo group, and what makes them more likely to have that response!

In the combo, 29% of the patients discontinued treatment due to side effects and with Everolimus alone, 12% discontinued.  However, both groups had large number of reduced dosages and/or dose interruptions, 89% in the combo group, and 54% in the evero group.  Read: some tough side effects.

The most serious side effect in my opinion was that renal failure occurred in 11% of patients in the combo, 5 of the 51 patients.  Grouping ‘renal impairment with failure”, the combo caused such problems in 18% of those patients, 12% i the evero group. Not good news for those of us with one kidney, so something to be monitorly VERY carefully.

The other ‘usual suspects’ in the side effects in the combo were hypertension 42% vs 10%, diarrhea 81% vs 19%.  Not surprising was a fairly high rate of ‘hemorrhagic events”, ie, bleeding problems in both groups, 32% vs 26%. And more.

Again, not easy, better than no treatments,or using everolimus alone.  All these meds demand good communication with the treating team and patients.  Sadly missing in this trial and in every other one is any real guidance as to which patients might best respond to this combo. Neither is there a neat comparison to the second-line use of Nivo or Cabo.  Practice, practice, and be aware of your own health issues as to side effect potential as you look at these trials and your own situation.

http://www.multivu.com/players/English/7690031-eisai-lenvima-fda-2/  for the company’s review and videos by Dr. Sumanta Pal at the City of Hope and a spokemans from Esai.


Filed under Clinical Trials, FDA Meds & Trials, Medications, Patient Resources, Targeted Therapies, Therapies

3 Responses to Lenvima/Lenvatinib with & without Everolimus–New FDA approval

  1. Thank you for this post Peggy. Absolutely agree that FDA approval was based on very scant data from Phase 2 trial. Lots of down-dosing for toxicities, so needs really careful, expert management and ongoing data collection. Do you have any sense of the PRICE for the combo? Surely not double…

    • Deb, I do not know about the price, and since all that really matters to the patient is the price which he must pay–all based on negotiated discounts which can be huge, it is nearly impossible to predict that.

      Still think the biggest concern I have is that this just no acknowledgement that all of these meds are given without an analysis of the molecular nature of the cancer. If these 150 or so patients were examined as to that, we might see trends or even some absolutes as with whom these med, Lenvatinib or Everolimus might be more effective. At the relative costs of the trial to the costs of the genomic analysis would make the testing very valuable, I can conclude that no one really want to know what will work with which patient, until it is absolutely mandatory to do so. What is happening in CA re genetic testing/molecular testing?

      • Hi Peggy,
        Agree with your comments about giving targeted therapies without knowing what targets to hit… I’m not sure how anyone would choose this combination. (On what basis? a biologic rationale for mTOR plus what?)
        re: your question
        “I can conclude that no one really want to know what will work with which patient, until it is absolutely mandatory to do so. What is happening in CA re genetic testing/molecular testing?”

        Slightly off topic, but:
        One thing that IS happening in Canada is the broad collection of RWE (Real World Evidence) for kidney cancer patients, from diagnosis to death. We (Kidney Cancer Canada) collaborated with our Kidney Cancer Research Network here to establish a huge registry/database that includes the medical records of approx 80% of rcc patients in Canada. (This db called CKCis — Canadian Kidney Cancer Information System). Some cancer centres are collecting tumour/blood tissues to go with the evolving records. While this is not PROSPECTIVE for decision-making yet, it is collecting some really valuable data about what is happening, and the huge variability in treatment choices/outcomes, along with outcomes data between institutions. As advocates we are involved and looking to track how private insurance does/doesn’t affect outcomes; how place of residence affects, etc.
        Specifically for genomic testing, I had mine done at no cost here, but patients have to ask and have some sort of rationale. (No actionable targets for me at this time.) Agree that all trials need to be collecting as much data about the tumour and the host as possible — otherwise we will continue to be shooting darts in the dark.

        Best to you Peggy. And thank you for all you do!

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