OBJECTIVES : Nivolumab+ipilimumab continues to show persistent, significant overall survival (OS) benefit versus sunitinib in 1L aRCC patients with I/P risk for more than five years, as demonstrated in CheckMate 214 (NCT02231749). This study assessed the stability of lifetime OS predictions for both treatment arms using trial data with a minimum of up to 5 years of follow-up.

METHODS : OS hazard ratios (HRs) were calculated for nivolumab+ipilimumab versus sunitinib with minimum 18, 24, 37, 42, and 60 months of follow-up. Parametric models, including traditional distributions and cubic splines were used to fit observed OS data. Extrapolations were corrected with background mortality, while model performance was evaluated based on the NICE DSU guidance 14 and 21. Stability of lifetime OS predictions was assessed by comparing extrapolation functional forms, and survival (mean and landmark rates) across all DBLs.

RESULTS : Across all DBLs, OS HRs were stable and the proportional hazards assumption was upheld, granting dependent modelling as the best option. The log-normal distribution consistently provided the best fit in both dependent and independent models, whereas the exponential and gamma distributions were the worst two fits. Log-normal fits to earlier DBLs slightly underestimated observed OS rates in later DBLs. Respectively, predicted 5-year OS rates using the 18-month DBL were 39.9% and 29.7% for nivolumab+ipilimumab and sunitinib, increasing to 41.9% and 31.6% using the 60-month DBL, and were conservative versus landmark trial OS. Mean lifetime OS estimations for nivolumab+ipilimumab and sunitinib increased by 0.56 and 0.45 life years using the 60-month versus the 18-month DBL.

CONCLUSIONS : Despite underestimations versus observed data from the 60-month DBL, the log-normal distribution remains the most appropriate functional form for both nivolumab+ipilimumab and sunitinib in all DBLs. Subsequent nivolumab use following sunitinib may explain appropriateness of the log-normal distribution and its ability to capture the hazard profile of the sunitinib arm.