Long-term follow-up of the pivotal CheckMate-214 trial showed that dual immunotherapy with nivolumab (Opdivo) plus ipilimumab (Yervoy) maintained a survival benefit over single-agent sunitinib in patients with advanced renal cell carcinoma (RCC).1
In CheckMate-214, 1096 patients with advanced RCC were randomized 1:1 to either nivolumab combined with ipilimumab or single-agent sunitinib. A conditional survival and 5-year follow-up analysis of the trial was presented at the 2021 ESMO Congress showing that 6% of the 547 evaluable patients treated with nivolumab/ipilimumab were continuing treatment compared with 2% of the 535 evaluable patients treated with sunitinib. Moreover, median duration of therapy was 7.9 (2.1-21.8) months in the nivolumab/ipilimumab arm and 7.8 (3.5-19.6) months in the sunitinib arm, and 55% of the intent-to-treat (ITT) population on nivolumab plus ipilimumab had subsequent systemic therapy compared with 68% in the sunitinib arm.
“With a median follow up of 67.7 months, conditional survival outcomes were analyzed post hoc and conditional survival was defined as the probability of a patient remaining alive, progression free or in response for an additional 2 years beyond annual landmark,” said lead researcher Robert J. Motzer, MD, Kidney Cancer Section Head, Genitourinary Oncology Service; and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center.
Efficacy in the ITT population showed superior OS in the nivolumab plus ipilimumab arm with a hazard ratio (HR) of 0.72. Five-year progression-free survival (PFS) probabilities with nivolumab plus ipilimumab versus sunitinib was 30% versus 14%, respectively. This outcome was also seen in the intermediate/poor-risk (I/P) population of 31% versus 11% in the combination and single agent arm, respectively, and also in the favorable-risk (FAV) population at 26% versus 21%.
Similar outcomes were seen when looking at the overall response rate (ORR) at 39% (95% CI, 35%-44%) with nivolumab plus ipilimumab versus 32% (95% CI, 29%-37%) with sunitinib in the ITT population and 42% (95% CI, 37%-47%) versus 27% (95% CI, 23%-31%) in I/P patients, respectively. In the FAV patient population, ORR was 30% (95% CI, 22%-38%) with nivolumab plus ipilimumab versus 52% (95% CI, 43%-61%) on sunitinib. A higher proportion of patients also achieved a complete response (CR) with nivolumab plus ipilimumab compared with sunitinib regardless of risk. In the ITT population, the ORR was 12% versus 3% on the nivolumab plus ipilimumab arm and sunitinib arm, respectively, compared with 11% vs 2% in the I/P arm and 13% versus 6% in the FAV population.
There were 9.6% of patients who achieved CR but did not progress with nivolumab plus ipilimumab versus 2.4% who progressed on sunitinib. Median duration of response was also longer with nivolumab plus ipilimumab in all 3 patient populations and more patients had ongoing responses with nivolumab plus ipilimumab across all risk groups (ITT, 63% vs 50%; I/P, 64% vs 50%; FAV, 59% vs 52%).
In the conditional survival analysis, the probability of patients remaining alive for an additional 2 years from the start of randomization of the treatments to the time of the analysis after 3 years increased in all patient populations.
In the ITT population, probability for survival increased from 71% to 81%, it increased from 66% to 79% in the I/P population, but the probability for an additional 2 years from survival remained at 85% for the FAV population. Conditional OS was also higher in the combination arm beyond the 3-year landmark analysis in all patients and regardless of their risk category (ITT, 81% vs 72%; I/P, 79% vs 72%; FAV, 85% vs 72%). Probability of remaining progression free had a higher increase at 37% to 89% in the ITT patient population, I/P patients saw a higher increase at 36% to 90% and FAV patients had the lowest increase of probability to remain progression free at 38% to 85%.
“Conditional OS estimates were consistently high with nivolumab plus ipilimumab in patients with complete response and improved from time 0 to 3 years in all clinical subgroups,” concluded Motzer. “The safety profile [with nivolumab plus ipilimumab] remained consistent with previous reports with a better health related quality of life comparison.”
1. Motzer R, Tannir N, McDermott D, et al. Conditional survival and 5-year follow-up in CheckMate 214: first-line nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma. Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021; virtual. Abstract 661P.