Deconstructing IO Therapy: Three Combinations,
Three Viewpoints from Key Opinion Leaders
Kidney Cancer Journal 81
n this wide-ranging discussion, three opinion leaders address
essential issues related to the use of immunotherapy
combinations in the frontline space for RCC. As they
compare the rationale for the use of these respective combinations,
each participant offers a unique perspective, including
key messages from the pivotal trials supporting IO
treatment. The particpants include Rana Mckay MD, Matthew
Milowsky, MD, and Thomas Powles, FRCP. The discussion
is chaired by Robert Figlin, MD, Editor-in-Chief of
Kidney Cancer Journal.
COMBINING IPILIMUMAB AND NIVOLUMAB
Dr Figlin: In the ever changing landscape for the management
of RCCa, please summarize the key takeaways from
the recent data on ipi/nivo in the frontline setting?
Dr Mckay: Data regarding nivo and ipi in patients with
metastatic RCC have dramatically changed the way we
approach newly diagnosed patients. For the first time,
we are challenging the treatment paradigm of frontline
TKI alone. The combination of nivo/ipi in a large randomized
phase 3 trial, CheckMate-214 was actually shown
to be superior to sunitinib and is one of the first studies
to demonstrate superiority of non-VEGF agents in the
frontline space. The big takeaway from this study—the
primary endpoint of the study was actually to look at objective
response, PFS, and overall survival in patients
with intermediate and poor-risk disease. The study included
about 51% of patients with intermediate risk
disease and 17% of patients with poor-risk disease.
When we look at the breakdown of patients with intermediate
and poor-risk disease we see a statistically significant
improvement in objective response rate with the
combination of nivo/ipi. What’s striking is that the complete
response rate was 9% in this patient population.
Additionally, there was an improvement in PFS and an
updated efficacy analysis showing it was statistically significant.
Overall survival was also superior to sunitinib
with a HR of 0.66 in the updated analysis which was statistically
significant and practice changing. While the
primary endpoint of the study did not evaluate favorable
risk disease, it’s important to look at the favorable risk
patients and try to understand what does the combination
of nivo/ipi do with this patient population. While
the objective response rate was higher with sunitinib
compared to nivo/ipi, when we look at that complete response
rate, we see that it is actually higher in the
nivo/ipi patients. The CR rate in favorable risk patients
in CheckMate-214 was around 6% in sunitinib-treated
patients but 11% in the nivo/ipi patients, suggesting that
there probably is a subset of patients with favorable risk
disease who may derive benefit from the combination of
nivo/ipi. Additionally, when looking at the intent to
treat population, nivo/ipi showed improved ORR, PFS,
and OS compared to sunitinib.
The other thing to point out is when we look at the
favorable risk patients who were enrolled in the Check-
Mate-214 we see an overperformance of the controlled
arm. The PFS of sunitinib-treated patients approaches
25.1 months, higher than frontline trials that used sunitinib
as a comparator arm. Nivo/ipi has certainly
changed the frontline space. It clearly has demonstrated
improved responses and survival for patients with advanced
diseease, and for the first time we see patients entering
durable remissions with IO combination therapy.
Dr Figlin: What populations of patients are best suited for
this approach in your practice?
Dr Mckay: At the present time, most of our biomarkers to
guide clinical decision marking are based on clinical parameters.
We have clinical risk stratification systems that
help inform prognosis and they have been utilized in
guiding treatment decisions, however these are not predictive.
Unfortunately, we do not have any soluble,
blood-based biomarkers that have proven to be validated
across mRCC. The combination nivo/ipi has demonstrated
efficacy for those with intermediate and poor risk
disease and those who are able to receive IO therapy and
do not have significant autoimmune disease that would
I
ROUNDTABLE
Rana Mckay,
MD1
Matthew
Milowsky, MD2
Thomas Powles,
FRCP3
1 Moores Cancer Center, University of California, San Diego, San Diego, California
2 UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
3 Barts Cancer Institute, London, England