Trastuzumab emtansine (T-DM1) in Asian patients with previously treated HER2-positive locally advanced (LA) or metastatic breast cancer (MBC): Data from the phase III EMILIA study

Abstract

Background The phase 3 EMILIA study (NCT00829166) was initiated based on phase 1 and 2 data identifying the HER2-targeted antibody-drug conjugate T-DM1 as a potential therapy for HER2-positive advanced breast cancer previously treated with trastuzumab (H) and taxane (T). We report a subgroup analysis of Asian patients enrolled in Asia.

Methods EMILIA, a randomized, open-label, phase 3 study, compared T-DM1 (3.6 mg/kg IV q3w) with capecitabine (C; 1000 mg/m2 po bid, days 1–14, q3w) plus lapatinib (L; 1250 mg/day po qd) in patients with HT-pretreated HER2-positive, LA/MBC. Cox proportional hazards models and the Kaplan-Meier method were used to estimate progression-free (PFS) and overall survival (OS) in Asian patients.

Results 76 and 82 patients from Korea, Taiwan, Singapore, Hong Kong, and The Philippines were randomized to CL and T-DM1, respectively (75 and 80 were safety evaluable). At a median follow up of 13 months, median PFS was 6.9 vs 9.3 months (HR, 0.72; 95% CI: 0.48–1.06) with CL vs T-DM1. Objective response rates (modified RECIST v1.0) were 38.7% (95% CI: 26.7–51.9) and 44.4% (95% CI: 31.9–57.5) with CL and T-DM1 respectively, with median response durations of 6.9 and 9.6 months. At the 2nd interim analysis, with a median follow up of 19 months, median OS was 22.7 vs 34.3 months (HR, 0.43; 95% CI: 0.24–0.77) with CL vs T-DM1. There was an increase in G3-G4 thrombocytopenia in the Asian subgroup (Table); safety profiles were otherwise similar. Table: 284P.

Adverse events (CTCAE v3.0; %) Global Asian CL (n=488) T-DM1 (n=490) CL (n=75) T-DM1 (n=80) ≥Grade (G) 3 57.0 40.8 54.7 60.0 Leading to discontinuation C: 9.4 L: 7.6 5.9 C: 4.0 L: 1.3 6.3 Thrombocytopenia G1 G2 G3 G4 1.8 0.8 0 0.2 6.9 9.6 11.2 2.7 1.3 0 0 0 3.8 5.0 30.5 8.8 Hemorrhage G1 G2 G3 G4 12.3 2.7 0.8 0 24.7 3.7 1.2 0.2 13.3 1.3 2.7 0 36.3 0 0 0

Conclusions T-DM1 conferred a clinically meaningful benefit compared with CL in Asian patients with HT-pretreated HER2-positive LA/MBC, which was generally consistent with that in the global population. Although generally similar to the global safety profile, increased G3 and G4 thrombocytopenia was noted with T-DM1 in Asian patients but there was no G>1 hemorrhage.

Clinical trial identification NCT00829166.

Editorial acknowledgement Medical writing support was provided by Tracy McNally, PhD, and Holly Strausbaugh, PhD, on behalf of Twist Medical, LLC, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study F. Hoffmann-La Roche Ltd.

Funding F. Hoffmann-La Roche Ltd.

Disclosure S. Im: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Hanmi; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Non-Financial Interests, Personal, Other, Investigational agent for trial: Dae Woong; Financial Interests, Personal, Advisory Board: GSK. I. Park: Financial Interests, Personal, Full or part-time Employment: Korea University Guro hospital National Cancer Center, Korea. J.H. Sohn: Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim. S.C. Lee: Financial Interests, Personal and Institutional, Invited Speaker: Pf