David A. Braun, MD, PhD

David A. Braun, MD, PhD, of Yale Cancer Center, was the formal discussant of the abstract on the 4-year follow-up of the CLEAR trial. “We have made remarkable progress [in advanced renal cell carcinoma] and are now in the combination era of immunotherapy-based therapy and immunotherapy-based doublets. The first-line setting is dominated by immunotherapy-based combinations,” he told listeners.

Dr. Braun commented on the high progression-free survival rates of immunotherapy plus tyrosine kinase inhibitor combinations and now an overall survival benefit in the CLEAR trial. “There is a wide separation [in survival curves] early on that gets narrower over time. This is difficult to understand because of subsequent therapy. The results raise the question of the durability of response. Median duration of response is about 2 years,” he said. “With nivolumab plus ipilimumab, response rates are lower, but those who achieve a response are still responding 3 to 5 years later.”

Dr. Braun continued: “These results do not change practice. They reaffirm it for intermediate- and poor-risk patients. We need more study for favorable-risk disease. Immunotherapy plus tyrosine kinase inhibitor responses do not lead to cures,” he commented.

“In my practice, for poor-risk, intermediate-risk patients, including those with metastatic disease or a sarcomatoid component, I favor nivolumab plus ipilimumab. For most patients who require a rapid response, I want high overall response rates and low progression-free survival rates and so would use an immunotherapy plus tyrosine kinase inhibitor combination. For durability of response, I would opt for nivolumab plus ipilimumab, where responses appear to be more durable.”

Dr. Braun posed a key question as to how best to treat a patient who experiences disease progression on a PD-L1 inhibitor. “It may be feasible to rechallenge with an immunotherapy plus tyrosine kinase inhibitor combination,” he noted. “There are no scientific polls on how practitioners are using these data. I posed the question on Twitter, and one-third of practitioners were using an immunotherapy plus tyrosine kinase inhibitor rechallenge after disease progression on an immune checkpoint inhibitor.” 

DISCLOSURE: Dr. Braun has stock and other ownership interests in Fortress Biotech; has served as a consultant or advisor to AbbVie, Adept Field Solutions, Aptitude Health, AVEO, Blueprint Partnership, Bristol Myers Squibb, Catenion, Cello Health, Charles River Associates, Dedham Group, Defined Health, Exelixis, Insight Strategy, Octane Co., Schlesinger Associates, Slingshot Insights, Targeted Oncology, and Trinity Group; has received research funding from AstraZeneca and Exelixis; and has received reimbursement for travel and accommodation expenses from Bristol Myers Squibb.