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Trastuzumab emtansine for HER2-positive advanced breast cancer.

Publication ,  Journal Article
Verma, S; Miles, D; Gianni, L; Krop, IE; Welslau, M; Baselga, J; Pegram, M; Oh, D-Y; Diéras, V; Guardino, E; Fang, L; Lu, MW; Olsen, S ...
Published in: N Engl J Med
November 8, 2012

BACKGROUND: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker. METHODS: We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted. RESULTS: Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with lapatinib plus capecitabine; P<0.001); results for all additional secondary end points favored T-DM1. Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine. CONCLUSIONS: T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. (Funded by F. Hoffmann-La Roche/Genentech; EMILIA ClinicalTrials.gov number, NCT00829166.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

November 8, 2012

Volume

367

Issue

19

Start / End Page

1783 / 1791

Location

United States

Related Subject Headings

  • Young Adult
  • Trastuzumab
  • Survival Rate
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Quinazolines
  • Neoplasm Metastasis
  • Middle Aged
  • Maytansine
  • Lapatinib
 

Citation

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Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., … EMILIA Study Group, . (2012). Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med, 367(19), 1783–1791. https://doi.org/10.1056/NEJMoa1209124
Verma, Sunil, David Miles, Luca Gianni, Ian E. Krop, Manfred Welslau, José Baselga, Mark Pegram, et al. “Trastuzumab emtansine for HER2-positive advanced breast cancer.N Engl J Med 367, no. 19 (November 8, 2012): 1783–91. https://doi.org/10.1056/NEJMoa1209124.
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783–91.
Verma, Sunil, et al. “Trastuzumab emtansine for HER2-positive advanced breast cancer.N Engl J Med, vol. 367, no. 19, Nov. 2012, pp. 1783–91. Pubmed, doi:10.1056/NEJMoa1209124.
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh D-Y, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K, EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783–1791.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

November 8, 2012

Volume

367

Issue

19

Start / End Page

1783 / 1791

Location

United States

Related Subject Headings

  • Young Adult
  • Trastuzumab
  • Survival Rate
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Quinazolines
  • Neoplasm Metastasis
  • Middle Aged
  • Maytansine
  • Lapatinib