Nicholas J. Vogelzang, MD, FASCO, FACP, medical
oncologist with Comprehensive Cancer
Centers of Nevada (CCCN). He serves as
Associate Chair of the Genitourinary Committee
for US Oncology Research. The author and coauthor
of hundreds of peer-reviewed articles in
the oncology literature, he serves as Vice Chair
of GU Committee SWOG, a worldwide network
of researchers that design and conduct cancer
clinical trials. Dr Vogelzang is also Clinical
Professor of Medicine at University of Nevada
School of Medicine as well as Clinical Professor
at UNLV School of Medicine, Las Vegas,
Nevada.
This is GU ASCO 2.0, a fresh, intuitive, yet
evidence-based analysis. In this wide ranging
interview, Dr Vogelzang drills beyond the data
to build a translational framework for interpreting
results presented at GU ASCO as he highlights the
potential impact of emerging results on clinical practice during
this interview with the Kidney Cancer Journal.
Q: Comparing this year’s meeting of GU ASCO to several
years of similar scientific sessions, what impressions did
you come away with this year? In your analysis last year
for the Kidney Cancer Journal you did not see any major
shift in the treatment paradigm. Was this year different?
Dr Vogelzang: Yes, I thought it was a very exciting time
in contrast to earlier years. The fact that avelumab/
axitinib and the pembrolizumab/axitinib studies were
presented and that the nivolumab/ipilimumab (nivo-ipi)
combination was updated made for a lot of hallway and
backroom discussion. We have all been looking for a bit
of advantage of one regimen over another and what we
would do in the ‘real world.’ When my colleagues and I
met at seminars with representatives from three major
companies, Eisai, Merck and Pfizer, they expressed excitement
as well.
Q: How would you characterize the obstacles that still
need to be overcome in clinical trials?
Dr Vogelzang: The crux of the matter is that we do not
have cross-trial comparisons. We have four dual agent
trials all of which were superior to the standard agent
sunitinib given on the 4/2 schedule—pembrolizumab/
axitinib, avelumab/axitinib, atezolizumab/bevacizumab
and nivo-ipi. If one compares them in a table format by
patient characteristics, primary and secondary end
points, there are multiple imbalances.
18 Kidney Cancer Journal
Q: If the comparisons are difficult to equate, what strikes
you from a clinical standpoint as most dramatic?
Dr Vogelzang: The bottom line on this is that avelumab/
axitinib and atezolizumab/bevacizumab did not hit (yet)
the overall survival endpoint. They hit PFS which is by
every account an FDA approvable endpoint. On the other
hand, pembrolizumab/axitinib not only hit
PFS but also hit an OS endpoint, which is
wonderful since the RCC research community
does not ordinarily achieve OS. Now, when
you look at nivo-ipi, it initially hit overall
survival in the intermediate and poor risk
subgroups of patients. Data presented at GU
ASCO provided some evidence for utilizing
nivo-ipi in good risk patients as well, because
of increased number of complete responses
compared with sunitinib, and the durability
of those complete responses. In his presentation and
based on these updated results from CheckMate 214,
Nizar Tannir recommended that nivo-ipi may be used for
all patients with mRCC, regardless of risk classification.
Dr Tannir indicated that OS was equivalent but that there
were more CRs in the nivo-ipi group vs sunitinib. What
is the upshot of the 2019 studies? It seems that pembrolizumab/
axitinib and nivo/ipi are the top 2 regi-
mens of choice because of their improvement in OS.
Avelumab/axitinib and atezolizumab/bevacizumab are
strong contenders because of their excellent tolerability
and PFS advantage. If they show a survival advantage
with future follow-up they will be considered equal to the
other regimens.
Q: It seems that we have gone far beyond the earlier
treatment algorithms that to a large degree dictated
therapeutic choices. It’s a far more complicated calculus
now. Can you delve a bit further into the relative merits
of PFS and OS with relation to patient subgroups and
the benefit of these therapies based on prognostic risk
factors? Isn’t PFS considered a surrogate marker for OS?
Dr Vogelzang: Yes, PFS is considered a surrogate for OS and
that’s what is sort of ironic. When the bar gets raised as
it has been lately, you start going beyond PFS per se to
consider factors such as the overall survival advantage for
nivo-ipi in pre-specified subgroups. In that context, and
bringing in data from the other studies, it looks like
pembrolizumab/axitinib had an OS advantage in all three
subgroups—favorable, intermediate and poor risk. The
intermediate risk group is the big category by percent and
none of the three studies subdivided the intermediates
into intermediate-favorable and intermediate-unfavorable
risk. The Italian group Iacovelli et al (Clin Genito-
CONFERENCE HIGHLIGHTS
GU ASCO 2019
Encapsulating Highlights Through the Lens of a Key Opinion
Leader With Insights, Forecasts and Take-Home Messages