Evaluation of Overall Response Rate and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Immunotherapy Trials

Purpose: With the approval of immuniotherapies for a variety of indications, methods to assess treatment benefit addressing the rest nose patterns loved are important. We evaluated RECIST criteria-based overall response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of ITS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immuniotherapies trials. Experimental Design: Thirteen randomized, multicenter, active-control trials containing immuniotherapies agents submitted to the FDA were analyzed. Associations between treatment effects of ORR, PFS, modified ITS, and OS were evaluated at individual and trial levels. Patient - level responder analysis was performed for PFS and OS. Results: The coefficient of determinination (R-2) measured the strength of associations, where values near 1 imply surrogacy and values close to 0 suggest no association. At the trial level, the association between hazard ratios (I IR) of ITS and OS was R-2 = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R-2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PTS and OS was 0.61. Trial-level associations between modified ITS and OS ranged between 0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of PFS and OS for responders versus nonresponders were 0.129195% confidence interval (CI), 0.11-0.15] and 0.118 (95% CI, 0.11 0.1 I ), respectively. Conclusions: Although responders exhibited longer survival and ITS than nonresponders, the trial-level and individual-level associations were weak between PFS/ORR and OS. Modifications to PTS did not improve associations. (C) 2018 AACR.