title: Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients.
abstract: OBJECTIVE
  To assess the validity of objective response to chemotherapy as a surrogate end point for survival in metastatic breast cancer.
  
  
  METHODS
  We carried out a meta-analysis on individual data from 2,126 metastatic breast cancer patients who were enrolled onto 10 randomized trials comparing standard versus intensified epirubicin-containing chemotherapy.
  
  
  RESULTS
  The intensified chemotherapy was associated with a significantly higher tumor response rate compared with standard chemotherapy (pooled odds ratio for nonresponse, 0.60; 95% CI, 0.51 to 0.72). The intensified regimens also led to better (although not significant) survival (pooled odds ratio, 0.94; 95% CI, 0.86 to 1.04; P = .22). Tumor response was a highly significant predictor of survival (P < .0001). When tumor response was introduced in the Cox model, the hazard ratio in favor of experimental treatment changed from 0.94 to 1.005 (95% CI, 0.91 to 1.11; P = .92), indicating that no residual effect of the experimental treatment on survival was present once tumor response was adjusted for. This suggests that the overall survival benefit of intensified epirubicin was a result of the increase in response rate. The median survival time of patients with complete response and partial response was 28.8 months (95% CI, 25.4 to 45.3 months) and 21.3 months (95% CI, 19.2 to 22.4 months), respectively; whereas, the median survival time of patients with no response was 14.6 months (95% CI, 13.9 to 15.4 months).
  
  
  CONCLUSIONS
  These results support the hypothesis that the achievement of an objective response to chemotherapy in metastatic breast cancer is associated with a true survival benefit. The potential role of objective response as a surrogate end point for survival in chemotherapy trials of metastatic breast cancer warrants further investigation.
authors.affiliation: Unit of Clinical Epidemiology, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132 Genoa, Italy. paolo.bruzzi@istge.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
authors.forename: Maria P
authors.initials: MP
authors.lastname: Sormani
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
authors.forename: Marco
authors.initials: M
authors.lastname: Danova
authors.forename: Christian
authors.initials: C
authors.lastname: Focan
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: James
authors.initials: J
authors.lastname: Paul
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rosso
authors.forename: Marco
authors.initials: M
authors.lastname: Venturini
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents