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.

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 24 Pg. 2600-8 (Aug 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26101239 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Breast Neoplasms (drug therapy, enzymology)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Female
• Humans
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (biosynthesis)
• Trastuzumab