Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31.

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.
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.
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).
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.
AuthorsKaren 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, Wendy R Parulekar
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 14 Pg. 1574-83 (May 10 2015) ISSN: 1527-7755 [Electronic] United States
PMID25779558 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright© 2015 by American Society of Clinical Oncology.
Chemical References
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Bridged Compounds
  • Quinazolines
  • Taxoids
  • lapatinib
  • taxane
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized (administration & dosage)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Biomarkers, Tumor (analysis)
  • Breast Neoplasms (chemistry, drug therapy, pathology)
  • Bridged Compounds (administration & dosage)
  • Diarrhea (chemically induced)
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Eruptions (etiology)
  • Female
  • Follow-Up Studies
  • Humans
  • International Cooperation
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Staging
  • Patient Selection
  • Quality of Life
  • Quinazolines (administration & dosage, adverse effects)
  • Receptor, ErbB-2 (analysis)
  • Taxoids (administration & dosage)
  • Trastuzumab
  • Treatment Outcome

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