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Medline ® Abstract for Reference 16

of 'Systemic treatment for metastatic breast cancer: General principles'

Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients.
Bruzzi P, Del Mastro L, Sormani MP, Bastholt L, Danova M, Focan C, Fountzilas G, Paul J, Rosso R, Venturini M
J Clin Oncol. 2005;23(22):5117.
PURPOSE: To assess the validity of objective response to chemotherapy as a surrogate end point for survival in metastatic breast cancer.
PATIENTS AND 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).
CONCLUSION: 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.
Unit of Clinical Epidemiology, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132 Genoa, Italy. paolo.bruzzi@istge.it