David McDermott, MD
Immunotherapy has made an incredible impact on the treatment of patients with metastatic renal cell carcinoma (RCC), and is now beginning to make waves in other settings of the disease.
However, though drugs such as nivolumab (Opdivo) have proven their worth as both a single agent and in combination, immunotherapy is not ideal for every patient with RCC, according to David F. McDermott, MD.
“We need to do a much better job of identifying predictive biomarkers—not just looking at immunohistochemistry, but RNA sequencing, and whole-exome sequencing,” said McDermott, director of the Biologic Therapy and Cutaneous Oncology Programs at Beth Israel Deaconess Medical Center.
McDermott chaired the Immunotherapy of Genitourinary Cancer session during the 2017 SUO Annual Meeting, which covered data on both single-agent immune checkpoint blockade and combination immunotherapy in RCC.
In an interview with OncLive during the meeting, McDermott shared some of the successes with immunotherapy in RCC and gave his insight on the future treatment of these patients.
OncLive: Can you please provide an overview of your talk?
McDermott: There are a lot of new interesting data in both kidney cancer and bladder cancer for immune-based therapies. We have established that single-agent immune checkpoint blockade with either PD-1/PD-L1 is active in both diseases, and now people are looking at other questions, such as, “How can you overcome resistance to treatment by adding new agents in?” For example, does CTLA-4 in addition to PD-1 add benefit? Does blocking VEGF in addition to blocking PD-1/PD-L1 add benefit? Importantly, how can we figure out which patients should get which combination? This is because most combinations add adverse events and costs, so it is up to us to try to identify who should get which new combination therapy ahead of time.
Combinations have been very successful in the metastatic setting. Could you comment on some of these combinations?
The newest and probably most exciting data come from the CheckMate-214 study, which looked at the combination of PD-1 blockade with nivolumab, and CTLA-4 blockade with ipilimumab (Yervoy), which is FDA approved in melanoma. However, this trial established its role in kidney cancer, particularly in the intermediate- and poor-risk population of patients based on clinical criteria. In that subgroup, patients who received the combination did better in terms of response, had a longer progression-free survival (PFS), and significantly longer overall survival. There was a higher complete response rate at approximately 9%, which is very exciting.
The toxicity is an issue; obviously, with combinations, it can be an issue. There were more treatment-related deaths on the CTLA-4/PD-1 combination of ipilimumab plus nivolumab, but there were actually fewer grade 3/4 toxicities. Approximately 60% of the patients who received this combination required steroids. Therefore, you must educate your team and your patients about managing these side effects. They can be managed, but they pose a challenge. The efficacy data are very exciting. We haven’t seen anything like this for frontline treatment and we are looking forward to its potential FDA approval in early 2018.
What are your thoughts on nivolumab as a single agent in RCC?
As you know, it is FDA approved for patients who have failed VEGF-targeted therapy in the second-line setting. We have long advocated to try to move it up to the frontline setting because it has a preferable therapeutic index and it has a pretty good toxicity profile for most patients with less than 10% having to come off for toxicity.
[Additionally] there is a small group of patients who get durable responses with treatment, sometimes even after the treatment stops. That percentage is low—it might only be 5% or 10%—but it would be exciting and important to move it up to the frontline setting for those patients so they might be able to skip some of the more toxic treatments. However, to do that, we need to do a much better job of identifying predictive biomarkers—not just looking at immunohistochemistry, but RNA sequencing and whole-exome sequencing, as well.