Combination Nivolumab/Ipilimumab Shows Long Term Survival in Conditional Survival Analysis of Advanced RCC

The combination therapy of nivolumab (Opdvio) plus ipilimumab (Yervoy) showed superior and lasting overall survival (OS) results versus sunitinib (Sutent) in a conditional survival analysis comparing 1,096 patients on either treatment with advanced renal cell carcinoma (RCC), according to data presented at the 2021 European Society for Medical Oncology (ESMO) Congress.1

The 1,096 patients with advanced RCC were randomized 1:1 to either nivolumab plus ipilimumab or sunitinib. At the 5-year follow up, 6% of the 547 patients treated with nivolumab plus ipilimumab were continuing treatment compared with 2% of the 535 patients treated with sunitinib. Moreover, median duration of therapy was 7.9 (2.1-21.8) months in the nivolumab plus 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,” lead researcher Robert J. Motzer, MD, explained in his ESMO presentation.

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.”

_Reference

_{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.}