Keywords: Oncology, PFS, OS, Immuno-Oncology, Go/No-Go, PTS
Progression-free survival is a popular end point in cancer drug development majorly due to the fact that it requires a smaller sample size and shorter follow-up. With overall survival remaining the gold standard endpoint for demonstrating clinical benefit, a better understanding of the relationship between PFS and OS is important not only for the sponsors to design oncology confirmatory trials also for the regulators to assess the benefit/risk profile of a novel therapy when only PFS results are available. Controversial findings have seen in justifying the surrogacy of PFS for OS when the tumor types, the magnitude of treatment effect, availability of subsequent therapy, and the time of survival post-progression vary. With the novel immune checkpoint and co-stimulatory drugs being actively evaluated in combination with chemotherapy and targeted therapy, the utility of PFS as a surrogate endpoint for OS becomes more complicated as delayed clinical effect may be seen. The discussions will be conducted to majorly focus on two questions- 1. How the relationship between PFS and OS can be best considered for the different study design components (e.g., treatment effect assumptions, IA/FA timing and boundaries, analysis method to characterize clinical benefit) when a registrational study protocol is developed? 2. How the relationship between PFS and OS can be best modelled in the simulation settings to help address the questions regarding the probability of technical success and the Go/No-Go decision?