• Karen A Gelmon, Frances M Boyle, Bella Kaufman, David G Huntsman, Alexey Manikhas, Angelo Di Leo, Miguel Martin, Lee S Schwartzberg, Julie Lemieux, Samuel Aparicio, Lois E Shepherd, Susan Dent, Susan L Ellard, Katia Tonkin, Kathleen I Pritchard, Timothy J Whelan, Dora Nomikos, Arnd Nusch, Robert E Coleman, Hirofumi Mukai, Sergei Tjulandin, Rustem Khasanov, Shulamith Rizel, Anne P Connor, Sergio L Santillana, Judith-Anne W Chapman, and Wendy R Parulekar.
• Karen A. Gelmon, David G. Huntsman, and Samuel Aparicio, British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver; Susan L. Ellard, British Columbia Cancer Agency, Cancer Centre for the Southern Interior, Kelowna, British Columbia; Julie Lemieux, Centre Hospitalier Affilié Hopital Du St Sacrement, Quebec City, Quebec; Lois E. Shepherd, Dora Nomikos, Judith-Anne W. Chapman, and Wendy R. Parulekar, NCIC Clinical Trials Group, Queen's University, Kingston; Susan Dent, Ottawa Health Research Institute, Ottawa; Kathleen I. Pritchard, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto; Timothy J. Whelan, Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario; Katia Tonkin, Cross Cancer Institute, Edmonton, Alberta, Canada; Frances M. Boyle, Patricia Ritchie Centre for Cancer Care and Research, Mater Hospital, North Sydney, New South Wales, Australia; Bella Kaufman, Sheba Medical Centre, Tel Hashomer; Shulamith Rizel, Rabin Medical Center, Petach Tikva, Israel; Alexey Manikhas, City Clinical Oncological Dispensery, St Petersburg; Sergei Tjulandin, Russian Cancer Research Center, Moscow; Rustem Khasanov, Clinical Oncology Dispensary, Kazan, Russia; Angelo Di Leo, Sandro Pitgliani Medical Oncology Unit, Prato, Italy; Miguel Martin, Servicio Oncologia Hospital Gregorio Marañon, Madrid, Spain; Lee S. Schwartzberg, West Clinic, Memphis, TN; Arnd Nusch, Praxis, Velbert, Germany; Robert E. Coleman, Weston Park Hospital, Cancer Research Centre, Sheffield, United Kingdom; Hirofumi Mukai, National Cancer Center Hospital East, Kashiwa-shi, Japan; Anne P. Connor, GlaxoSmithKline, Collegeville, PA; and Sergio L. Santillana, GlaxoSmithKline, Rio de Janeiro, Brazil. kgelmon@bccancer.bc.ca.
• J. Clin. Oncol. 2015 May 10; 33 (14): 1574-83.

PurposeThe efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown.Patients And MethodsThe MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors.ResultsFrom July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03).ConclusionAs first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane.© 2015 by American Society of Clinical Oncology.

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