Karen A Gelmon1, Frances M Boyle2, Bella Kaufman2, David G Huntsman2, Alexey Manikhas2, Angelo Di Leo2, Miguel Martin2, Lee S Schwartzberg2, Julie Lemieux2, Samuel Aparicio2, Lois E Shepherd2, Susan Dent2, Susan L Ellard2, Katia Tonkin2, Kathleen I Pritchard2, Timothy J Whelan2, Dora Nomikos2, Arnd Nusch2, Robert E Coleman2, Hirofumi Mukai2, Sergei Tjulandin2, Rustem Khasanov2, Shulamith Rizel2, Anne P Connor2, Sergio L Santillana2, Judith-Anne W Chapman2, Wendy R Parulekar2. 1. 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. 2. 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.
Abstract
PURPOSE: The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positivemetastatic breast cancer (BC) is unknown. PATIENTS AND METHODS: The 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. RESULTS:From 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). CONCLUSION: As 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.
RCT Entities:
PURPOSE: The 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 METHODS: The 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. RESULTS: From 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). CONCLUSION: As 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.
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Authors: Martine Piccart-Gebhart; Eileen Holmes; José Baselga; Evandro de Azambuja; Amylou C Dueck; Giuseppe Viale; Jo Anne Zujewski; Aron Goldhirsch; Alison Armour; Kathleen I Pritchard; Ann E McCullough; Stella Dolci; Eleanor McFadden; Andrew P Holmes; Liu Tonghua; Holger Eidtmann; Phuong Dinh; Serena Di Cosimo; Nadia Harbeck; Sergei Tjulandin; Young-Hyuck Im; Chiun-Sheng Huang; Véronique Diéras; David W Hillman; Antonio C Wolff; Christian Jackisch; Istvan Lang; Michael Untch; Ian Smith; Frances Boyle; Binghe Xu; Henry Gomez; Thomas Suter; Richard D Gelber; Edith A Perez Journal: J Clin Oncol Date: 2015-11-23 Impact factor: 44.544