Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer
By S. Verma, D. Miles, L. Gianni, Ian Krop, M. Welslau, J. Baselga, M. Pegram, D. Oh, V. Diéras, E. Guardino and 4 more. New England Journal of Medicine, 2012
3,357 citations recorded by the source corpus.
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 adverse events of grade 3 or above 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.)
Subfields: Cancer Research, Oncology
View Paper: https://www.semanticscholar.org/paper/c1be35f92224ac905e2e1e8f3ca86cfe88316f09
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Citations in the corpus
- Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications (2014, positive): “The study showed a significantly prolonged progression-free survival and overall survival with less toxicity than lapatinib plus capecitabine [73].”
- Antibody-drug conjugates: recent advances in conjugation and linker chemistries (2016, background): “, 2010), and trastuzumab emtansine (Kadcyla) in 2013 for HER2-positive breast cancer (LoRusso et al., 2011; Verma et al., 2012).”
- ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2) (2014, background): “lapatinib plus capecitabine in the subset of 118 patients who were randomized in the first-line setting, having relapsed on or within 6 months of adjuvant trastuzumab, appeared similar to the effect seen in the overall trial [100].”
- Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. (2014, background): “This will become an increasingly important issue in an era with a growing array of effective anti-HER2 agents available for clinical use [9–11].”