Efficacy of adjuvant trastuzumab (T) compared with no T for patients (pts) with HER2-positive breast cancer and tumors ≤ 2cm: A meta-analysis of the randomized trastuzumab trials.

Breast Cancer - HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - HER2/ER
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 508)
Ciara Catherine Maria O'Sullivan, Ian Bradbury, Evandro De Azambuja, Edith A. Perez, Priya Rastogi, Marc Spielmann, Heikki Joensuu, Karla V. Ballman, Joseph P. Costantino, Suzette Delaloge, Dimitrios Zardavas, Martine J. Piccart-Gebhart, JoAnne Zujewski, Eileen McCormick Holmes, Richard D. Gelber; National Cancer Institute, Bethesda, MD; Frontier Science, Kincraig, United Kingdom; Institut Jules Bordet, Brussels, Université Libre de Bruxelles, Brussels, Belgium; Mayo Clinic, Jacksonville, FL; University of Pittsburgh Medical Center, Pittsburgh, PA; Institut Gustave Roussy, Villejuif, France; Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; Mayo Clinic, Rochester, MN; Biostatistical Center, National Surgical Adjuvant Breast and Bowel Project and Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA; Institut de Cancerologie Gustave Roussy, Villejuif, France; Jules Bordet Institute, Breast International Group, Brussels, Belgium; Frontier Science (Scotland), Inverness-Shire, Scotland; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA

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Abstract Disclosures


Background: Adjuvant T plus chemotherapy improves disease-free survival (DFS) and overall survival (OS) vs. chemotherapy alone for pts with early stage HER2-positive breast cancer. We conducted a meta-analysis to estimate DFS and OS for pts with small tumors (≤2cm) in the T arms from 5 of the 6 randomized adjuvant trastuzumab trials. Pts with tumors ≤2cm, with 0 or 1 positive lymph nodes, and hormone receptor (HR) positive disease had a 5-year DFS of 91% and a 5-year OS of 97% (O’Sullivan, SABCS 2013; abstract:1327). We now plan to conduct an additional meta-analysis to assess the efficacy of T compared with no T for pts with small tumors (≤2cm). Methods: Six randomized controlled trials (RCT) were identified by a Medline search from 2004-2013. Trial groups from 5 phase III RCTs provided data (HERA, NCCTG N9831, NSABP B31, PACS 04, and FinHER).In total, 11,200 pts were randomized in these 5 trials;4,220 of whom had ≤2cm tumors, and known number of positive axillary lymph nodes and HR status(2,588 randomized to T and 1,632 to no T). The individual pt meta-analysis will include pts with tumors ≤2 cm (T1a, T1b and T1c) and 0-1, 2-3 and ≥ 4 positive lymph nodes. Separate analyses will be performed for the two HR cohorts. This analysis will complement the published summary data-based Cochrane Review (Moja et al. 2012) by allowing a detailed investigation of the effect of disease characteristics, such as HR, on treatment effects. In addition to the standard Yusuf-Peto fixed effects model (Yusuf et al. 1985) we will investigate the impact of heterogeneity in study baseline hazards and study treatment effects by fitting random effect models.An intention to treat approach will produce a conservative effect estimate as substantial numbers of control-group pts 'crossed over' to the T arm after positive DFS results were reported. Methods to account for this ‘selective crossover’ are being developed; we plan to extend these methods to the meta-analysis setting to provide less conservative estimates. Results: Pending. Conclusions: A meta-analysis of 5 randomized adjuvant T trials focusing on pts with tumors ≤2cm will be performed and results submitted before the meeting.