Acknowledging there are now expanded therapeutic choices in the first-line setting for advanced renal cell carcinoma, formal study discussant Camillo Porta, MD, of the University of Bari Aldo Moro, Italy, said that studies of the immunotherapy combinations could not be compared directly. “We should avoid direct comparisons between studies that have different agents, different endpoints, different populations, different prognostic groups, different distribution of patients in risk groups, and differences in results,” he cautioned.

“It is reasonable if one aims at an earlier survival benefit, an immune checkpoint inhibitor plus a VEGF tyrosine kinase inhibitor would presumably be an optimal choice. Side effects of the different combinations differ. Safety events for nivolumab/ipilimumab are limited to the induction phase, whereas with an immune checkpoint inhibitor plus a VEGF tyrosine kinase inhibitor, they persist over time due to prolonged administration,” Dr. Porta continued. “For nivolumab/cabozantinib, adverse events can be managed by dose reduction of cabozantinib.”

Camillo Porta, MD

Answers Sought to Guide Treatment Decisions

There are many unanswered questions to guide therapeutic decisions. “There is the possibility of using a VEGF tyrosine kinase inhibitor for a limited time. In the case of aggressive disease, the use of an immune checkpoint inhibitor plus a VEGFR tyrosine kinase inhibitor seems reasonable to try to control disease while waiting for the tail effect of immunotherapy,” proposed Dr. Porta.

“It is unrealistic to hope for a comparative trial [of newly available regimens]. We will need to play with the data we have and figure out how to proceed. I do not feel that a potentially useful trial will ever be done. We are exploring the biologic basis of immunotherapies plus other combinations, and these insights will drive our practice,” Dr. Porta commented. More data will be forthcoming from the COSMIC 313 trial, the CLEAR trial, and the A031704 PDIGREE trial. 

DISCLOSURE: Dr. Porta has served as an advisor or consultant to GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Schering-Plough, Pfizer, Roche, and Novartis; has served on a speakers bureau for GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Schering-Plough, Pfizer, Roche, and Novartis; and has received research funding from Bayer HealthCare Pharmaceuticals, Schering-Plough, and Novartis.