Correlation between overall survival and other endpoints in metastatic breast cancer with second- or third-line chemotherapy: Literature-based analysis of 24 randomized trials

Summary Background and objective Correlations between overall survival (OS) and other endpoints have been evaluated in patients with metastatic breast cancer (MBC) who received first-line chemotherapy. However, no corresponding analysis has been accomplished for patients who have undergone second- or third-line chemotherapy. Methods We evaluated the potential of progression-free survival (PFS)/time to progression (TTP) and objective response rate (ORR) as surrogates of OS when OS data were not available. Correlations were evaluated by Spearman's rank correlation coefficient ( r s ) and weighted linear regression model. Subgroup analyses were performed for previous chemotherapy, regimen, study endpoint, study period and HER2 status. Results Twenty-four randomized trials involving 8617 patients were included for analysis. The correlation between PFS/TTP and OS was 0.7824 (95% CI: 0.6034–0.8702), whereas ORR did not strongly correlate with OS ( r s  = 0.5398, 95%CI: 0.2942–0.7233). Further, the association between hazard ratios (HRs) of PFS/TTP and OS of the 22 randomized studies showed a moderate correlation ( r s  = 0.5725, 95%CI: 0.1735–0.8277); the slope of the regression model ( β ) was 0.5366 (95%CI: 0.3479–0.7253). In particular, the PFS/OS correlation for HER2-positive MBC patients was stronger ( r s  = 0.9515, 95%CI: 0.7009–1.0000; β  = 0.8728, 95%CI: 0.0795–1.6661). Conclusions These results suggest that PFS/TTP is a useful early endpoint for patients with MBC who have undergone second- or third-line chemotherapy, especially for those who are HER2-positive.