Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients

Bruzzi, P., Del Mastro, L., Sormani, M., Bastholt, L., Danova, M., Focan, C., Fountzilas, G., Paul, J. , Rosso, R. and Venturini, M. (2005) Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients. Journal of Clinical Oncology, 23(22), pp. 5117-5125. (doi: 10.1200/JCO.2005.02.106)

Abstract

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.

• Item Type: Articles
• Additional Information: 26th Annual San Antonio Breast Cancer Symposium, SAN ANTONIO, TX, DEC 03-06, 2003
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paul, Mr James
• Authors: Bruzzi, P., Del Mastro, L., Sormani, M., Bastholt, L., Danova, M., Focan, C., Fountzilas, G., Paul, J., Rosso, R., and Venturini, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Clinical Oncology
• ISSN: 0732-183X