Patients with advanced renal cell carcinoma receiving first-line therapy with a checkpoint inhibitor combination of nivolumab plus ipilimumab experienced over twice as long treatment-free survival without toxicity compared with patients receiving the targeted therapy sunitinib, according to data analysis from the randomized phase III CheckMate 214 trial. Clinical trials investigating checkpoint inhibitors should assess treatment-free survival to describe quality of survival time for clinical decision-making when initiating therapy, said the study authors. The study by Regan et al is published in Clinical Cancer Research.

Study Methodology

The researchers evaluated treatment-free survival in the CheckMate 214 randomized phase III trial of nivolumab plus ipilimumab vs sunitinib for treatment-naive patients with advanced renal cell carcinoma. The analysis included all study patients—550 who received the checkpoint inhibitors and 546 who received sunitinib. Treatment-free survival was estimated by the 42-month restricted mean items defined by the area between Kaplan-Meier curves for two time-to-event endpoints defined from randomization: time to protocol therapy cessation and time to subsequent systemic therapy initiation or death.

Treatment-free survival was subdivided as occurring with and without toxicity by counting days with at least one grade ≥ 3 treatment-related adverse event.

Results

The researchers found that over a 42-month period, 52% and 39% of patients with intermediate/poor risk were alive after receiving nivolumab plus ipilimumab and sunitinib, respectively; 18% and 5% surviving treatment-free, respectively. Among favorable-risk patients, 70% and 73% of the patients receiving nivolumab plus ipilimumab and sunitinib, respectively, were alive; 20% and 9% were treatment-free.

Over the 42-month period, mean treatment-free survival was over twice as long after nivolumab plus ipilimumab than sunitinib for patients with intermediate/poor risk (6.9 vs 3.1 months, respectively) and three times as long for patients with favorable risk (11.0 and 3.7 months, respectively). The mean treatment-free survival with grade ≥ 3 treatment-related adverse events was a small proportion of time for both treatments (0.6 vs 0.3 months after nivolumab plus ipilimumab vs sunitinib for intermediate/poor risk, and 0.9 vs 0.3 months for patients with favorable risk).

“Patients initiating first-line nivolumab plus ipilimumab for advanced renal cell carcinoma spent more survival time treatment-free without toxicity vs those on sunitinib, regardless of risk group,” concluded the study authors.

Translational Relevance

In a statement commenting on the study’s results, first author Meredith M. Regan, ScD, Associate Professor at Harvard Medical School and Dana-Farber Cancer Institute, said, “As we continue to develop new treatments, we have an opportunity to think about new methods to better balance the efficacy and toxicity to patients. To do that, we needed a new endpoint to quantify those two aspects together—to continue to improve survival for patients while also focusing on how they are spending their time. That’s how [treatment-free survival] came to be.”

Dr. Regan, of Harvard Medical School and Dana-Farber Cancer Institute, is the corresponding author of this study.

Disclosure: Funding for this study was provided by Bristol Myers Squibb, Ono Pharmaceutical Company Ltd., the National Cancer Institute, and a Dana-Farber/Harvard Cancer Center National Institutes of Health SPORE Grant. For full disclosures of the study authors, visit https://clincancerres.aacrjournals.org.