Pooled analysis of candidate surrogate endpoints for overall survival in treatment-naïve metastatic melanoma treated with ICIs

Using surrogate endpoints for overall survival (OS) may expedite the development of novel treatments. Pooled analysis of 1865 patients in four randomized controlled CheckMate trials of first-line single-agent nivolumab or combinations of nivolumab and ipilimumab versus dacarbazine or immunotherapy for metastatic melanoma evaluated three candidate surrogates for OS: objective response rate (ORR, progression-free survival (PFS), and time to next treatment or death (TNTD). At the individual level, ORR exhibited a strong correlation with OS, whereas PFS and TNTD showed a moderate level correlation with OS. At trial level, the key requirement for validating surrogates, all candidate surrogates demonstrated moderate predictive abilities for OS in future trials. Compared with PFS, TNTD displayed a slightly stronger correlation with OS at both patient and trial levels. The authors conclude that evaluation ORR, PFS, and TNTD as surrogate endpoints may enable earliers prediction of OS benefit for first-line anti-PD-1 with or without anti-CTLA-4 regimens.