TDM-1 results reported @ ASCO annual mtg 2012 now in New England Journal of Medicine

[Lani]

EMILIA study-- good media coverage/ publicity may help sway FDA


N Engl J Med. 2012 Oct 1. [Epub ahead of print]
Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer.
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; the EMILIA Study Group.
Source

From Sunnybrook Odette Cancer Centre, Toronto (S.V.); Mount Vernon Cancer Centre, Northwood, United Kingdom (D.M.); San Raffaele Hospital, Milan (L.G.); Dana-Farber Cancer Institute (I.E.K.) and Massachusetts General Hospital (J.B.) - both in Boston; Medical Office Hematology, Aschaffenburg, Germany (M.W.); University of Miami Sylvester Comprehensive Cancer Center, Miami (M.P.); Seoul National University College of Medicine, Seoul, South Korea (D.-Y.O.); Institut Curie, Paris (V.D.); Genentech, South San Francisco, CA (E.G., L.F., M.W.L., S.O.); and Duke University Medical Center, Durham, NC (K.B.).
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 .).

PMID:
23020162