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.