Correlation of ORR and PFS with OS outcomes in phase III trials of immunotherapy in advanced NSCLC: Systematic review...

The ability of progression-free survival (PFS) and overall response rate (ORR) to predict overall survival (OS) outcomes in cancer trials is matter of debate. Herein, we investigated whether PFS and ORR predicted OS results in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in advanced NSCLC.

ORR (OR_ORR,%ORR), OS (HR_OS,mOS) and PFS (HR_PFS,mPFS) data were collected from phase III RCTs investigating ICIs in advanced NSCLC. Linear regression, weighted by sample size, between surrogate endpoints and OS were calculated. The power of correlation was defined by the value of coefficient of determination R² (≥0.7 strong, 0.69-0.50 moderate, <0.5 weak).

Forty investigational arms of ICIs ± chemotherapy (ChT) were identified for further investigation. Arm-level analysis revealed that mPFS had a strong correlation with mOS in all comparisons (R²=0.71), in ICIs+ChT trials (R²=0.81) and in first-line setting (R²=0.71). A weak correlation was found between mPFS-mOS (R²=0.48) in trials of ICIs without chemotherapy. Next, trial-level analysis revealed a weak correlation between HR_OS and HR_PFS in all different groups, except in ICIs+ChT trial (R²=0.60). In addition, based on arm-level analysis, mOS and %ORR had moderate correlation in all comparisons (R²=0.58), in ICIs+ChT (R²=0.58) or ICIs (R²=0.53). In trial-level analysis, OR_ORR and HR_OS had moderate correlation (R²=0.55) in first-line setting and a strong correlation in ICIs+ChT trials (R²=0.79).

Across trials investigating ICIs in advanced NSCLC, PFS and ORR demonstrated various degrees of relationship with OS. Caution should be taken when efficacy of novel ICIs regimens is evaluated only using surrogate outcomes.