LBA12 - Updated Overall Survival Results from EMILIA, a phase 3 study of trastuzumab emtansine (T-DM1) vs capecitabine (X) and lapatinib (L) in HER2-positiv...

Date 01 October 2012
Event ESMO Congress 2012
Session Breast cancer, metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Sunil Verma
Authors S. Verma1, D. Miles2, L. Gianni3, I. Krop4, M. Welslau5, J. Baselga6, M. Pegram7, D. Oh8, V. Dieras9, E. Guardino10, L. Fang11, M. Lu12, S. Olsen12, K. Blackwell13
  • 1Medical Oncology, Sunnybrook Odette Cancer Center, M4N 3E6 - Toronto/CA
  • 2Medical Oncology, Mount Vernon Cancer Center, HA6 2 RN - Northwood/UK
  • 3Medical Oncology, San Raffaele Hospital, 20132 - Milano/IT
  • 4Breast Oncology Center, Dana-Farber Cancer Institute, Boston/US
  • 5Praxis Dr. Klausmann / Dr. Welslau, DE-63739 - Aschaffenburg/DE
  • 6Hematology/oncology, Massachusetts General Hospital, MA 02114 - Boston/US
  • 7Sylvester Comprehensive Cancer Center, University of Miami, Miami/US
  • 8Department Of Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 9Department Of Medical Oncology, Clinical Trial Unit, Institut Curie, 75005 - Paris/FR
  • 10Breast Medical Oncology, Genentech, Inc., South San Francisco/US
  • 11Biostatistics, Genentech, South San Francisco/US
  • 12Global Development, Genentech, Inc., South San Francisco/US
  • 13Hematology/oncology Department, Duke University Medical Center, Durham/US

Abstract

Background

T-DM1 is an antibody–drug conjugate incorporating the HER2–targeted antitumor properties of trastuzumab (T) with the cytotoxic activity of the microtubule inhibitor DM1, conjugated by a stable linker.

Methods

Patients (pts) with confirmed HER2+ MBC (IHC3+ and/or FISH+) and prior treatment with T and a taxane were randomized to T-DM1 (3.6 mg/kg IV q3w) or X (1000 mg/m2 bid, days 1–14 q3w) + L (1250 mg PO qd, days 1-21). Primary end points were progression-free survival (PFS) by independent review, overall survival (OS), and safety. An interim OS analysis occurred at the time of the final PFS analysis.

Results

991 pts were enrolled; 978 received treatment. Median durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) mos. Baseline demographics, prior therapy, and disease characteristics were balanced. PFS was significantly improved with T-DM1; the interim OS analysis favored T-DM1, but the interim efficacy boundary was not crossed (see Table). PFS benefit was observed in most subgroups, including line of MBC therapy (1st, 2nd, 3rd, or later), type of prior treatment received, menopausal status, hormone receptor status, number of disease sites, race, and age, although the subgroup of pts >75 yrs old was too small to confirm benefit. Results for secondary end points, including objective response rate, clinical benefit rate, and time to treatment failure, favored T-DM1. T-DM1 was well tolerated and was associated with fewer grade =3 adverse events (AEs; 40.8% vs 57.0%). The incidence rates of cardiac AEs and left ventricular dysfunction were low and similar in both arms.

T-DM1
n=495
XL
n=496
PFS, median mos 9.6 6.4
HR (95% CI)

0.650 (0.549, 0.771)

P value <0.0001
Interim OS, median mos Not reached 23.3
HR (95% CI)

0.621 (0.475, 0.813)

P value 0.0005
Efficacy boundary: HR=0.617 or P=0.0003
OS, % (95% CI)
1-year

84.7 (80.8, 88.6)

77.0 (72.4, 81.5)

2-year 65.4 (58.7, 72.2) 47.5 (39.2, 55.9)
Objective response (OR), % (95% CI) 43.6 (38.6, 48.6) 30.8 (26.3, 35.7)
Duration of response in pts with OR, median mos (95% CI) 12.6 (8.38, 20.76) 6.5 (5.45, 7.16)
Clinical benefit rate, % (95% CI) [CR + PR + SD =6 mos] 58.2 (53.3, 63.1) 44.2 (39.2, 49.2)
Time to treatment failure, median mos 7.9 5.8
HR (95% CI) 0.703 (0.602, 0.820)
T-DM1
n=490
XL
n=488
Dose reduction, % 16.3

X 53.4 (n=487)

L 27.3 (n=488)
Grade =3 AEs, % 40.8 57.0
Cardiac dysfunction AE, % 0.8 2.3
LVEF <50% and =15-point decrease from baseline, % 1.7 (n=481) 1.6 (n=445)

Conclusions

T-DM1 conferred a significant and clinically meaningful improvement in PFS compared with XL. Results of other study end points, including interim OS, safety, and key secondary end points, favor T-DM1 and establish its role as a potential new therapy for HER2+ MBC pts previously treated with T and a taxane.