Heterogeneity in Survival with Immune Checkpoint Inhibitors and Its Implications for Survival Extrapolations: A Case Study in Advanced Melanoma.

Given that short clinical trial follow-up periods and survival heterogeneity introduce uncertainty in the health technology assessment of oncology therapies, this study evaluated the suitability of conventional parametric survival modeling approaches as compared with more flexible models in the context of immune checkpoint inhibitors that have the potential to provide lasting survival benefits.This study used extended follow-up data from the phase III CheckMate 067 trial (NCT01844505) to assess the predictive accuracy of standard parametric models in comparison with more flexible methods for estimating the long-term survival benefit of the immune checkpoint inhibitor combination of nivolumab plus ipilimumab in advanced melanoma.Mixture cure, parametric mixture, and landmark response models provided more accurate estimates of long-term overall survival versus external data than other models tested.In this case study with immune checkpoint inhibitor therapies in advanced melanoma, extrapolation models that explicitly incorporate differences in cancer survival between observed or latent subgroups showed greater accuracy with both early and later data cuts than other approaches did.