Vicki Goodman, MD
Topline results from the phase III CheckMate-214 trial showed that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) improved the objective response rate (ORR) and duration of response compared with sunitinib (Sutent) in patients with treatment-naïve metastatic renal cell carcinoma (RCC).
Bristol-Myers Squibb (BMS), the manufacturer of both drugs, announced the findings in a press release. The combination of the PD-1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab met the coprimary endpoint of ORR versus sunitinib, at 41.6% versus 26.5%. Median duration of response was 18.17 months in the sunitinib group. Patients in the combination arm had not yet reached the median duration of response.
Median progression-free survival (PFS) was 11.56 months (95% CI, 8.71-15.51) for the combination versus 8.38 months (95% CI, 7.03-10.81) for sunitinib, but investigators reported that the difference was not statistically significant (hazard ratio, 0.82; 95% CI, 0.64-1.05; stratified 2-sided P
“We are encouraged by the totality of the CheckMate-214 data,” Vicki Goodman, MD, development lead, Melanoma and Genitourinary Cancers, BMS, said in a press release. “The overall response rate and durability of response favored the combination of Opdivo and Yervoy, and the trend for PFS supports the potential of the combination in intermediate and poor-risk advanced renal cell carcinoma, the most common type of kidney cancer. This is an important study in first-line renal cancer as these patients need new options.”
The study will continue as planned to allow the third coprimary endpoint of overall survival (OS) to mature. The company plans to release full results at a future medical meeting.
RCC is the most common type of kidney cancer in adults and accounts for more than 100,000 deaths worldwide each year. The disease is most prevalent in Europe and North American, and the global 5-year rate of survival is 12.1%.
CheckMate-214 is a randomized, open-label study. Roughly 1070 previously untreated patients with advanced or metastatic RCC at 184 health centers in 28 countries are taking part in the trial.
Patients were randomly assigned to 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for 4 doses, followed by nivolumab at 3 mg/kg every 2 weeks, or 50 mg of sunitinib once daily for 4 weeks, followed by 2 weeks off, continuously. Both arms received treatment until progression or unacceptable toxicity.
The primary endpoints of the trial are PFS, OS, and ORR in an intermediate to poor-risk patient population.
The combination proceeded to phase III testing based on results from the phase I CheckMate-016 trial, which showed that patients with mRCC assigned to the combination had a 40.4% ORR and a 2-year OS rate of nearly 70%.
Investigators observed a 2-year OS rate of 67.3% for patients assigned to 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab (n = 47) in the 3-arm trial. Results from the trial showed that efficacy outcomes were similar for a group of patients assigned to 1 mg/kg of nivolumab plus 3 mg/kg ipilimumab (n = 47), but that group experienced a higher rate of adverse events (AEs).
A third arm of 6 patients assigned to nivolumab at 3 mg/kg plus ipilimumab at 3 mg/kg were censored at the time of analysis due to progression or dose-limiting toxicity.
Half of patients in the study had metastases that progressed on previous therapy.
Bristol-Myers Squibb has not released safety data from CheckMate-214. In CheckMate-016, 43 patients (91.5%) in the 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab group had treatment-related AEs of any grade, and 18 (38.3%) experienced grade 3 or 4 treatment-related AEs. Eleven patients (23.4%) in the 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab arm had a treatment-related serious AE. Researchers did not observe any grade 5 treatment-related AEs.
Single-agent nivolumab is currently approved by the FDA as a treatment for patients with metastatic RCC following prior antiangiogenic therapy.
Hammers HJ, Plimack ER, Infante JR, et al. Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma: the CheckMate 016 study [published online July 5, 2017]. J Clin Oncol. doi: 10.1200/JCO.2016.72.1985.