Correlations Between Progression-free Survival, Objective Response Rate, and Overall Survival in Clinical Trials of PD-1/PD-L1 Immune Checkpoint Blockade: A Meta-analysis.

Correlations Between Progression-free Survival, Objective Response Rate, and Overall Survival in Clinical Trials of PD-1/PD-L1 Immune Checkpoint Blockade: A Meta-analysis. Clin Pharmacol Ther. 2020 Jun 21;: Authors: Ye J, Ji X, Dennis PA, Abdullah H, Mukhopadhyay P Abstract PD-1/PD-L1 immune checkpoint blockade (ICB) has improved overall survival (OS) in solid tumor trials; however, parallel improvements in RECIST-based surrogate endpoints, progression-free survival (PFS) and objective response rate (ORR), are not always observed. Here, we assess the surrogacy of PFS/ORR for OS with ICB therapy across advanced/metastatic tumors. In a trial-level analysis (N = 40 randomized trials), PFS, ORR, and OS treatment effects were correlated (Spearman's rho). In a patient-level analysis, data were extracted from available trials of durvalumab; the correlation of PFS and OS was evaluated (Bayesian normal-induced-copula-estimation model) and the ordinal association between objective response and OS hazard ratio (HR) were assessed with concordance index measures. High correlation was observed between PFS HR and OS HR in intention-to-treat (ITT) (rho=0.76) and PD-L1-enriched populations (0.74); modest (or limited) benefit in PFS was associated with meaningful improvement in OS. Moderate correlations were observed between ΔORR and OS HR: ITT, -0.63; PD-L1-enriched, -0.53. At the patient level, a positive association was observed between PFS and OS...
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Pharmacol Ther Source Type: research