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Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer

Cited 2752 time in Web of Science Cited 3095 time in Scopus
Authors

Verma, Sunil; Miles, David; Gianni, Luca; Krop, Ian E.; Welslau, Manfred; Baselga, Jose; Pegram, Mark; Oh, Do-Youn; Dieras, Veronique; Guardino, Ellie; Fang, Liang; Lu, Michael W.; Olsen, Steven; Blackwell, Kim

Issue Date
2012-11
Publisher
Massachusetts Medical Society
Citation
New England Journal of Medicine, Vol.367 No.19, pp.1783-1791
Abstract
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.)
ISSN
0028-4793
URI
https://hdl.handle.net/10371/212818
DOI
https://doi.org/10.1056/NEJMoa1209124
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  • College of Medicine
  • Department of Medicine
Research Area DNA 손상 반응 타겟 물질의 면역조절 효과, Effect of DNA damage response target substances on immunomodulatory action, Efficacy and biomarker validation studies of targeted therapeutics, Resistance mechanisms according to targeted therapeutics, 표적 항암제 내성 기전 연구, 표적 항암제의 효과 검증 및 바이오마커 규명

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