Annual Meeting Proceedings II - Newly Released Abstracts for
BREAST CANCER—HER2/ER LBA1 Plenary Session, Sun, 1:00 PM-4:00 PM Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. Kimberly L. Blackwell, David Miles, Luca Gianni, Ian E. Krop, Manfred Welslau, José Baselga, Mark D. Pegram, Do-Youn Oh, Veronique Dieras, Steven R. Olsen, Liang Fang, Michael W. Lu, Ellie Guardino, Sunil Verma; Duke University Medical Center, Durham, NC; Mount Vernon Cancer Centre, Middlesex, United Kingdom; San Raffaele Hospital, Milan, Italy; Dana-Farber Cancer Institute, Boston, MA; Praxis Aschaffenburg, Aschaffenburg, Germany; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Medical Oncology, Institut Curie, Paris, France; Genentech, South San Francisco, CA; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada Background: T-DM1 is an antibody-drug conjugate comprising T, a stable linker, and the potent cytotoxic agent DM1; it incorporates the antitumor activities of T and the HER2-targeted delivery of DM1. Methods: EMILIA is a randomized study of T-DM1 vs XL, the only approved combination for T-refractory HER2� MBC. Patients (pts) received T-DM1 (3.6 mg/kg IV q3w) or X (1000 mg/m 2 PO bid, days 1–14 q3w) � L (1,250 mg PO daily) until progressive disease (PD) or unmanageable toxicity. Pts had confirmed HER2� MBC (IHC3� and/or FISH�), and prior therapy with T and a taxane. Primary end points were PFS by independent review, OS and safety. An interim OS analysis (efficacy boundary: HR� 0.617; p�0.0003) was planned at the time of the final PFS analysis. Results: 991 pts were enrolled; 978 received treatment. Median (med) durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) months (mo). Baseline demographics, prior therapy and disease characteristics were balanced. There was a significant improvement in PFS favoring T-DM1 (med 9.6 vs 6.4 mo; HR�0.650 [95% CI, 0.549–0.771]; p �0.0001). The med T-DM1 OS was not reached vs 23.3 mo (HR�0.621 [95% CI, 0.475–0.813]; p�0.0005); the interim efficacy boundary was not crossed. T-DM1 was well tolerated with no unexpected safety signals. The most common grade �3 adverse events (AEs) per treatment were for T-DM1: thrombocytopenia (12.9% vs 0.2%), increased AST (4.3% vs 0.8%), and increased ALT (2.9% vs 1.4%); for XL: diarrhea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0) and vomiting (4.5% vs 0.8%). The table lists other end points. Conclusions: T-DM1 conferred a significant and clinically meaningful improvement in PFS compared with XL. Other end points support T-DM1 as an active and well-tolerated novel therapy for HER2� advanced BC. T-DM1 XL OS, % (95% CI) 1-year 84.7 (80.76–88.55) 77.0 (72.40–81.50) 2-year Objective response (OR) 65.4 (58.65–72.15) 47.5 (39.20–55.89) % (95% CI) 43.6 (38.6–48.6) 30.8 (26.3–35.7) Duration of response in pts with OR, med mo (95% CI) 12.6 (8.38–20.76) 6.5 (5.45–7.16) Dose reduction, % 16.3 X 53.4 L 27.3 AEs > grade 3, % 40.8 57.0 © 2012 American Society of Clinical Oncology. Reprinted with permission.