Hazard ratio of progression-free survival is an excellent predictor of overall survival in phase III randomized controlled trials evaluating the first-line chemotherapy for extensive-disease small-cell lung cancer

Background: Whether hazard ratio (HR) of progression-free survival (HRpfs), odds ratio (OR) of response rate (ORrr), OR of disease control rate (ORdcr), and OR of 1-year overall survival (ORos1y) used for extensive-disease small-cell lung cancer (ED-SCLC) correlate with HR of overall survival (HRos) at a randomized-trial level, especially for a trial that evaluates molecular-targeted therapy (MTT) or immune checkpoint inhibitor (ICI), is unclear. Methods: We included an individually randomized controlled trial (RCT) comparing two regimens as the first-line treatment for chemo-naive ED-SCLC, which have been reported in English-language since 2000. A weighted Spearman's rank correlation coefficient (r) was evaluated. Results: We finally found 42 eligible articles consisted of 11,478 cases. Estimated r with HRos were as followings: HRpfs (29 trial, 8,573 cases, r=0.87), ORrr (39 trials, 11,030 cases, r=0.47), ORdcr (29 trials, 7,799 cases, r=0.48), and ORos1y (40 trials, 11,250 cases, r=0.69). Phase III subgroup (16 trials, 7,079 cases) yielded an excellent r between HRpfs and HRos of 0.96. ORdcr presented the best correlation with HRos for phase II trial subgroup (r=-0.64); however, this result was mainly calculated from MTT trials. HRpfs may overestimate the efficacy of MMT in a phase II trial. ORrr and ORdcr might undervalue the efficacy of ICI even in a phase III trial. Conclusions: HRpfs can be a good surrogate of HRos, especially in a phase III trial. Depending on a single outcome in a randomized phase II trial may result in unneeded phase III trial or inappropriate abandonment of the regimen.