David F. McDermott, MD
Nivolumab (Opdivo) has significantly impacted the treatment landscape of renal cell carcinoma (RCC), as it has improved survival as well as quality of life for patients with advanced disease.
The potential for the PD-1 inhibitor, which was approved by the FDA in advanced RCC based on findings from the CheckMate-025 trial in November 2015, has only continued to grow since it first hit the market. A recent analysis, which looked at long-term data from phase I and phase II clinical trials of single-agent nivolumab in RCC, found that one-third of patients were still alive at 4 and 5 years. In addition, responses were shown to be consistent across patient subgroups.
These findings are significant, says David F. McDermott, MD, director of the Biologic Therapy Program at Beth Israel Deaconess Medical Center.
“Compared to what we were dealing with 5 or 10 years ago with kidney cancer, these are encouraging data,” he says. “The interesting thing about nivolumab is that this may have an impact on a broader range of patients. Obviously, we need to look at it in the phase III trial and we will need more maturity of that data, but it is very promising.”
In an interview with OncLive
, McDermott provides further insight on the long-term efficacy and safety of nivolumab and its role in RCC. He also discusses potential combination regimens, as well as challenges with sequencing nivolumab.
OncLive: What were the goals of your analysis?
: In the phase III CheckMate-025 trial, nivolumab was significantly superior to everolimus (Afinitor) in patients who had failed prior antiangiogenic therapy, with improvements in overall survival (OS), quality of life, and safety. However, the follow-up on that trial was relatively short, with a minimum of 14 months.
The question we tried to address looking at the phase I and phase II trials was, with longer follow-up, what might we see in the phase III trial? This was a way of potentially looking into the future. We looked at the outcomes of about 200 patients who were treated on the phase I and phase II studies, and we found some interesting things. For example, the median OS was 22 months in the phase I and II trials. Now, with over 48 months of follow-up on both trials, approximately one-third of patients were alive at 4 years. In the phase II trial, where we have 5 years of follow-up, one-third of patients were alive, as well.
Then, we started comparing what we saw in subsets of patients in those trials with what we saw in the phase III trial. We looked at some clinical characteristics as they related to long-term outcome on the phase I and II trials. What we found was that neither prognostic group, initial response, or performance status seemed to predict which patients would be alive at 4 years. This means that we saw survivals in all subgroups, which is very interesting to us. You would think that survival would be lower in patients who had poor-risk disease, progression as their best response, or reduced performance status.
What did you learn in terms of the safety profile of nivolumab?
When you give an immunotherapy for 2 years or more, there is a question as to what the toxicity will look like. Interestingly, similar to how the responses happen early within the first 6 months, so does most of the toxicity. If you look behind 6 months in the phase I and II trials, the toxicity incidence seems to decrease. Out beyond 30 months in the phase II trial, we didn’t observe any treatment-related adverse events. That is encouraging for patients who need chronic therapy to remain in benefit. They are not accumulating significant toxicities—at least not on that trial.
Do you think nivolumab is here to stay in RCC?
Absolutely. The phase III trial is about the cleanest study that we have ever had in kidney cancer. We saw clear improvements in OS, quality of life, and safety. They were meaningful improvements—not just statistically significant improvements. Patients benefit from a chance not just for long-term survival, but a benefit that lasts when the drug is stopped.