title: Correlation between overall survival and other endpoints in metastatic breast cancer with second- or third-line chemotherapy: Literature-based analysis of 24 randomized trials.
abstract: 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 (rs) 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 (rs=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 (rs=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 (rs=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.
authors.affiliation: Ningbo University, Medical School, Department of Preventive Medicine, Ningbo, Zhejiang, PR China. Electronic address: liuliya@nbu.edu.cn.
authors.forename: Liya
authors.initials: L
authors.lastname: Liu
authors.affiliation: Nanjing Medical University, School of Public Health, Department of Epidemiology and Biostatistics, Nanjing, Jiangsu, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Ningbo University, Medical School, Department of Preventive Medicine, Ningbo, Zhejiang, PR China.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Nanjing Medical University, School of Public Health, Department of Epidemiology and Biostatistics, Nanjing, Jiangsu, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016014:Linear Models; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018709:Statistics, Nonparametric; D043823:Taxoids / Q000627:therapeutic use; D013997:Time Factors; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D043823:Taxoids; D000068258:Bevacizumab; D000068878:Trastuzumab
keywords: Breast cancer; Cancer du sein; Chimiothérapie; Objective response rate; Progression-free survival; Subsequent chemotherapy; Survie globale; Survie sans progression; Taux de réponse; Time to progression