Elizabeth Plimack, MD
Recent pivotal findings in the field of genitourinary malignancies, specifically renal cell carcinoma (RCC) and bladder cancer, demonstrate the burgeoning role of immunotherapy in the field.
Such data include the CheckMate-025 study results presented during the 2016 ASCO Annual Meeting, which showed that approximately one-third of patients with advanced RCC who were treated with single-agent nivolumab (Opdivo) in the second-line setting or later were still alive at 4 and 5 years. This was found in long-term follow-up results of phase I and phase II clinical trials of the PD-1 inhibitor.
“For the majority of patients [with RCC], they will likely get immunotherapy at some point in the trajectory of their disease, whether it’s early as part of an ongoing clinical trial, in second-line with the indication of nivolumab, or [later],” explains Elizabeth Plimack, MD.
In the field of bladder cancer, the FDA-approved PD-L1 inhibitor atezolizumab (Tecentriq) has generated excitement as a promising immunotherapy agent, while clinical trials have explored the durable activity of others, including durvalumab and nivolumab. Nivolumab was granted a breakthrough therapy designation by the FDA in this space in June 2016.
In an interview with OncLive
, Plimack, who is the director of Genitourinary Clinical Research at Fox Chase Cancer Center, discussed some of the most impressive advancements with immunotherapy agents in the fields of RCC and bladder cancer, as well as remaining questions with the use of these treatments.
OncLive: Focusing first on kidney cancer, what are some exciting data we have seen recently with nivolumab in this space?
: The most exciting data with nivolumab that was presented at the 2016 ASCO Annual Meeting was looking at long-term survival from some of the very earliest studies—phase I/II studies—that are the first studies to test nivolumab in kidney cancer. Nivolumab is now approved by the FDA for kidney cancer, but long-term follow-up requires a lot of time.
Now we have had, in some cases, 4 to 5 years of follow-up on the patients on these trials. What is really impressive to us is that one-third of patients are alive at 4 and 5 years. It looks like the term “durable responses” is actually one we can say now, knowing that we are looking at those long-term survival rates.
The other interesting thing is that those long-term benefits occurred in patients regardless of their initial response to therapy. These are progressors, including those with stable disease and response. It occurred regardless of risk group, even those poor-risk patients who typically have the worst prognosis. In some of those, the trajectory of their cancer can really be turned around, it seems, by nivolumab.
Some of that long-term survival is contributed to by additional developments in the world of kidney cancer. Some of those patients either have or will get these other drugs that have been developed over this long period of time. However, all of it just indicates significant progress in the field of kidney cancer, which we’re excited about.
What other questions with nivolumab still need to be answered in kidney cancer?
There are many, many other questions. The CheckMate-025 study, which was a randomized phase III trial of nivolumab versus everolimus (Afinitor), is a prime opportunity for biomarker development. When you have a randomized trial, you can look to see what is predictive over prognostic. That is one opportunity.
We are looking at how adverse events related to response is critical, to see if those patients tend to do worse or better. We need to also conduct a variety of other secondary analyses. For example, treatment beyond progression was a hot topic at this year’s ASCO. There is a lot to still learn to optimize how we use this drug.