Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer

Final results of NCIC CTG MA.31

Karen A. Gelmon, Frances M. Boyle, Bella Kaufman, David G. Huntsman, Alexey Manikhas, Angelo Di Leo, Miguel Martin, Lee 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 & 7 others Sergei Tjulandin, Rustem Khasanov, Shulamith Rizel, Anne P. Connor, Sergio L. Santillana, Judith Anne W. Chapman, Wendy R. Parulekar

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1574-1583
Number of pages10
JournalJournal of Clinical Oncology
Volume33
Issue number14
DOIs
StatePublished - May 10 2015

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Breast Neoplasms
Disease-Free Survival
Therapeutics
Neoplasms
Trastuzumab
taxane
human ERBB2 protein
lapatinib
Taxoids
Intention to Treat Analysis
Exanthema
Diarrhea
Neoplasm Metastasis
Survival
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer : Final results of NCIC CTG MA.31. / Gelmon, Karen A.; Boyle, Frances M.; Kaufman, Bella; Huntsman, David G.; Manikhas, Alexey; Di Leo, Angelo; Martin, Miguel; Schwartzberg, Lee; Lemieux, Julie; Aparicio, Samuel; Shepherd, Lois E.; Dent, Susan; Ellard, Susan L.; Tonkin, Katia; Pritchard, Kathleen I.; Whelan, Timothy J.; 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.

In: Journal of Clinical Oncology, Vol. 33, No. 14, 10.05.2015, p. 1574-1583.

Research output: Contribution to journalArticle

Gelmon, KA, Boyle, FM, Kaufman, B, Huntsman, DG, Manikhas, A, Di Leo, A, Martin, M, Schwartzberg, L, Lemieux, J, Aparicio, S, Shepherd, LE, Dent, S, Ellard, SL, Tonkin, K, Pritchard, KI, Whelan, TJ, Nomikos, D, Nusch, A, Coleman, RE, Mukai, H, Tjulandin, S, Khasanov, R, Rizel, S, Connor, AP, Santillana, SL, Chapman, JAW & Parulekar, WR 2015, '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 of Clinical Oncology, vol. 33, no. 14, pp. 1574-1583. https://doi.org/10.1200/JCO.2014.56.9590
Gelmon, Karen A. ; Boyle, Frances M. ; Kaufman, Bella ; Huntsman, David G. ; Manikhas, Alexey ; Di Leo, Angelo ; Martin, Miguel ; Schwartzberg, Lee ; Lemieux, Julie ; Aparicio, Samuel ; Shepherd, Lois E. ; Dent, Susan ; Ellard, Susan L. ; Tonkin, Katia ; Pritchard, Kathleen I. ; Whelan, Timothy J. ; 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. / Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer : Final results of NCIC CTG MA.31. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 14. pp. 1574-1583.
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title = "Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: Final results of NCIC CTG MA.31",
abstract = "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.",
author = "Gelmon, {Karen A.} and Boyle, {Frances M.} and Bella Kaufman and Huntsman, {David G.} and Alexey Manikhas and {Di Leo}, Angelo and Miguel Martin and Lee Schwartzberg and Julie Lemieux and Samuel Aparicio and Shepherd, {Lois E.} and Susan Dent and Ellard, {Susan L.} and Katia Tonkin and Pritchard, {Kathleen I.} and Whelan, {Timothy J.} and Dora Nomikos and Arnd Nusch and Coleman, {Robert E.} and Hirofumi Mukai and Sergei Tjulandin and Rustem Khasanov and Shulamith Rizel and Connor, {Anne P.} and Santillana, {Sergio L.} and Chapman, {Judith Anne W.} and Parulekar, {Wendy R.}",
year = "2015",
month = "5",
day = "10",
doi = "10.1200/JCO.2014.56.9590",
language = "English (US)",
volume = "33",
pages = "1574--1583",
journal = "Journal of Clinical Oncology",
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TY - JOUR

T1 - Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer

T2 - Final results of NCIC CTG MA.31

AU - Gelmon, Karen A.

AU - Boyle, Frances M.

AU - Kaufman, Bella

AU - Huntsman, David G.

AU - Manikhas, Alexey

AU - Di Leo, Angelo

AU - Martin, Miguel

AU - Schwartzberg, Lee

AU - Lemieux, Julie

AU - Aparicio, Samuel

AU - Shepherd, Lois E.

AU - Dent, Susan

AU - Ellard, Susan L.

AU - Tonkin, Katia

AU - Pritchard, Kathleen I.

AU - Whelan, Timothy J.

AU - Nomikos, Dora

AU - Nusch, Arnd

AU - Coleman, Robert E.

AU - Mukai, Hirofumi

AU - Tjulandin, Sergei

AU - Khasanov, Rustem

AU - Rizel, Shulamith

AU - Connor, Anne P.

AU - Santillana, Sergio L.

AU - Chapman, Judith Anne W.

AU - Parulekar, Wendy R.

PY - 2015/5/10

Y1 - 2015/5/10

N2 - 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.

AB - 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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