Kidney Cancer Journal 51
Dr Vogelzang: Yes there is. I would refer our readers to an
Editorial in the New England Journal of Medicine by Motzer
and Russo (June 3, 2018 DOI: 10.1056/ NEJMe1806331).
It reflects my views and is an excellent analysis and interpretation
of the results from the CARMENA trial. It emphasizes
the need to appropriately select patients for
either modality.
Q. How would you frame the current discussion about the
treatment algorithm for RCC after the ASCO meeting?
What are some of the pitfalls in selecting various strategies?
Dr Vogelzang: Based on the ASCO meeting, the treatment
paradigm is not changing yet. The biggest problem is that
insurance companies are still not reimbursing for the ipinivo
(ipilimumab and nivolumab) combination and we
have no definitive data on frontline IO agents (nivolumab
or pembrolizumab) given as monotherapy. The phase 2
data on pembrolizumab frontline were very encouraging.
I participated in that study and I had very good results
with it. So that is an encouraging step forward because
we now have upfront information on this agent. We
don’t have upfront nivolumab data. We have very strong
upfront ipilimumab/nivolumab but a lot of us are unable
to use it because of insurance issues.
Q. There was considerable speculation at ASCO about the
need for using a checkpoint inhibitor as the comparator
arm vs combination regimens with checkpoint inhibition.
Would you agree that there is a need for such study?
Dr Vogelzang: Yes, that would be very helpful. Let’s look
at the landscape of therapy: we have 2 combos (nivo/ipi
and atezolizumab/bevacizu-mab) that are superior to
sunitinib. We have a 3rd com-bo (avelumab/axitinib) that
has been compared to sunitunib but not yet reported. We
have five IO agents (nivolu-mab, pembrolizumab, atezolizumab,
durvalumab and avel- umab) and at least three
TKIs that will template well
with them. These TKIs are axitinib,
lenvatinib, and cabozantinib.
Cabozantinib seems
to be the most difficult to give
in combination with an IO.
Lenvatinib is also a bit tough
to administer with an IO because
of adverse effects, namely
hypertension and significant
diarrhea. Axitinib seems
clinically easiest to combine
but these are my own subjective
opinions.
Q. What are your thoughts on
first-line options at this point?
Once again, how does your
real-world experience line up
with the data being presented?
Dr Vogelzang:We have participated in the phase 2 of pembrolizumab
and lenvatinib, so this combination is a contender
for first line. There were quality-of-life data
presented at ASCO 2018 for atezolizumab and bevacizumab
that were quite promising based on a presentation
by Bernard Escudier. That should be considered as a
first-line therapy whether or not the patient has undergone
a nephrectomy. In addition there is the avelumab/
axitinib combination, and then there is nivolumab
and cabozantinib. We have seen promising results reported
in the JAVELIN Renal 100 Study for avelumab plus
axitinib. The safety profile of the combination avelumab
plus axitinib in treatment-naive patients with advanced
RCC seems to be manageable and consistent with that of
each drug alone, and the preliminary data on antitumor
activity are encouraging. This was reported by Toni
Choueiri and his team in the Lancet Oncology. (Vol.
19:451–460; April 2018) A phase 3 trial is assessing
avelumab and axitinib compared with sunitinib monotherapy.
Q. Is there a consensus on which of these combinations
seems to have the inside track for first line therapy?
Dr Vogelzang: These are all established regimens now and
it’s very difficult to know which of them is best. When I
am forced to, for one reason or another, I usually decide
to use nivolumab and axitinib or nivolumab and
cabozantinib. I do that because nivolumab is currently
the only IO that is covered by insurance.
Q. Then to what extent are you using the ipi-nivo regimen?
Dr Vogelzang: So far I’ve only treated 2 patients because
ipi-nivo is expensive, not covered by most 3rd parties and
only recently was put on the NCCN compendium. Over