LAUSR

e14122 Background: Our objective was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate end points for overall survival (OS) among patients with advanced non-small-cell lung cancer (NSCLC) in randomized trials of immunotherapy. Methods: Individual patient data (total N = 569 patients) were available from two multicentre, randomized, phase II/III trials (POPLAR and OAK). Analysis of OS, PFS and ORR were computed using the Kaplan-Meier estimates method and compared with the log-rank test, hazard ratios [HRs] and 95% confidence intervals [CIs] were calculated by using the Cox regression model. The surrogacy was evaluated using Spearman’s correlation coefficient (ρ) and coefficient of determination ( R²) between treatment effects on the surrogate end point and OS. We further validated the surrogacy in trial-level analysis with 26 NSCLC immunotherapy trials (total N = 12,094 patients) published prior to June 2018. Results: In the patient-level analyses, patients who achieved a response had better OS compared with nonresponders (HR 0.18; 95% CI, 0.11 to 0.29; P < 0.001). Greater OS was also observed in landmark anlyses at 6-month PFS (HR 0.21; 95% CI 0.11 to 0.39; P < 0.001) and 12-month PFS (HR 0.16; 95% CI 0.11 to 0.24; P < 0.001). PFS correlated with OS at the individual level (Spearman ρ = 0.37; P < 0.001). In the trial-level analysis, PFS moderately correlated with OS (Spearman ρ = 0.64; P < 0.001), and the R² was 0.50 (95% CI 0.39 to 0.64). Conclusions: In NSCLC immunotherapy trials, responders and patients with longer PFS had better OS. ORR and PFS are acceptable surrogates for OS in trials of immunotherapy, but caution must be taken when interpreting efficacy in the absence of OS data.