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

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  • 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.


  • Gelmon, Karen A
  • Boyle, Frances M
  • Kaufman, Bella
  • Huntsman, David G
  • Manikhas, Alexey
  • Di Leo, Angelo
  • Martin, Miguel
  • Schwartzberg, Lee S
  • Lemieux, Julie
  • Aparicio, Samuel
  • Shepherd, Lois E
  • Dent, Susan
  • Ellard, Susan L
  • Tonkin, Katia
  • Pritchard, Kathleen I
  • Whelan, Timothy
  • Nomikos, Dora
  • Nusch, Arnd
  • Coleman, Robert E
  • Mukai, Hirofumi
  • Tjulandin, Sergei
  • Khasanov, Rustem
  • Rizel, Shulamith
  • Connor, Anne P
  • Santillana, Sergio L
  • Chapman, Judith-Anne W
  • Parulekar, Wendy R

publication date

  • May 10, 2015

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