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

Paolo Bruzzi, Lucia Del Mastro, Maria P. Sormani, Lars Bastholt, Marco Danova, Christian Focan, George Fountzilas, James Paul, Riccardo Rosso, Marco Venturini

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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.

Original languageEnglish
Pages (from-to)5117-5125
Number of pages9
JournalJournal of Clinical Oncology
Volume23
Issue number22
DOIs
Publication statusPublished - 2005

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Biomarkers
Breast Neoplasms
Drug Therapy
Survival
Epirubicin
Neoplasms
Odds Ratio
Proportional Hazards Models
Meta-Analysis
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients. / Bruzzi, Paolo; Del Mastro, Lucia; Sormani, Maria P.; Bastholt, Lars; Danova, Marco; Focan, Christian; Fountzilas, George; Paul, James; Rosso, Riccardo; Venturini, Marco.

In: Journal of Clinical Oncology, Vol. 23, No. 22, 2005, p. 5117-5125.

Research output: Contribution to journalArticle

Bruzzi, P, Del Mastro, L, Sormani, MP, Bastholt, L, Danova, M, Focan, C, Fountzilas, G, Paul, J, Rosso, R & Venturini, M 2005, 'Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients', Journal of Clinical Oncology, vol. 23, no. 22, pp. 5117-5125. https://doi.org/10.1200/JCO.2005.02.106
Bruzzi, Paolo ; Del Mastro, Lucia ; Sormani, Maria P. ; Bastholt, Lars ; Danova, Marco ; Focan, Christian ; Fountzilas, George ; Paul, James ; Rosso, Riccardo ; Venturini, Marco. / Objective response to chemotherapy as a potential surrogate end point of survival in metastatic breast cancer patients. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 22. pp. 5117-5125.
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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.",
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AU - Del Mastro, Lucia

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AU - Bastholt, Lars

AU - Danova, Marco

AU - Focan, Christian

AU - Fountzilas, George

AU - Paul, James

AU - Rosso, Riccardo

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N2 - 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.

AB - 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.

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