Efficacy of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2-positive early breast cancer and tumors ≤ 2 cm: A meta-analysis of the randomized trastuzumab trials

Ciara C. O'Sullivan, Ian Bradbury, Christine Campbell, Marc Spielmann, Edith A. Perez, Heikki Joensuu, Joseph P. Costantino, Suzette Delaloge, Priya Rastogi, Dimitrios Zardavas, Karla V. Ballman, Eileen Holmes, Evandro De Azambuja, Martine Piccart-Gebhart, Jo Anne Zujewski, Richard D. Gelber

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59 Scopus citations

Abstract

Purpose: We compared efficacy of trastuzumab versus no trastuzumab in patients with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) -positive breast cancer treated in randomized trials. Methods: A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) -positive and HR-negative cohorts. Random effect models and Yusuf-Peto fixed effects models assessed the impact of heterogeneity on baseline hazards and treatment effects across studies. Peto-Pike cumulative incidence estimates were stratified by study and nodal status. Results: Median follow-up time was 8 years. For 2,263 patients with HR-positive disease, 8-year cumulative incidence rates comparing trastuzumab versus no trastuzumab were 17.3% versus 24.3% (P < .001) for DFS and 7.8% versus 11.6% (P = .005) for OS, respectively; for 1,092 HR-positive patients with zero or one positive lymph nodes, results were 12.7% versus 19.4% (P = .005) for DFS and 5.3% versus 7.4% (P = .12) for OS, respectively. For 1,957 patients with HR-negative disease, 8-year cumulative incidence rates were 24.0% versus 33.4% (P < .001) for DFS and 12.4% versus 21.2% (P < .001) for OS, respectively; for 1,040 HR-negative patients with zero or one positive lymph nodes, results were 20.4% versus 26.3% (P = .05) for DFS and 8.2% versus 12.2% (P = .084) for OS, respectively. Conclusion: Women with HER2-positive tumors ≤ 2 cm in the randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastuzumab. Trastuzumab-treated patients with HR-positive disease and ≤ one positive lymph node may be candidates for trials assessing less aggressive treatment approaches.

Original languageEnglish (US)
Pages (from-to)2600-2608
Number of pages9
JournalJournal of Clinical Oncology
Volume33
Issue number24
DOIs
StatePublished - Aug 20 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    O'Sullivan, C. C., Bradbury, I., Campbell, C., Spielmann, M., Perez, E. A., Joensuu, H., Costantino, J. P., Delaloge, S., Rastogi, P., Zardavas, D., Ballman, K. V., Holmes, E., De Azambuja, E., Piccart-Gebhart, M., Zujewski, J. A., & Gelber, R. D. (2015). Efficacy of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2-positive early breast cancer and tumors ≤ 2 cm: A meta-analysis of the randomized trastuzumab trials. Journal of Clinical Oncology, 33(24), 2600-2608. https://doi.org/10.1200/JCO.2015.60.8620