A trial-level and patient level analyses to study the association between the efficacy endpoints, ORR, PFS and OS, for immunotherapies
*Sirisha Mushti, FDA, CDER 

Keywords: progression free survival, overall survival, trial level association

In the recent years, a significant number of immunotherapies have been approved by FDA for lung, melanoma, renal cell and many other caner types. Our experience with immunotherapies states that progression-free survival may not be an appropriate surrogate for overall survival and there seems be a benefit in overall response rate across all these indications. In this research work, we attempt to study the association of progression-free survival, and overall response rate with overall survival by considering the randomized, active-controlled trials having an adequate sample size to perform the analyses. A separate analysis for each cancer type and a pooled analysis across all cancer types will be considered. The trial-level associations using the progression-free survival hazard ratio, overall survival hazard ratio, and overall response rate odds ratio will be studied using weighted linear regression model and a patient level responder analysis is performed to study the association between progression-free survival, and overall survival.