Abstract 284P
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: 9.4L: 7.6 | 5.9 | C: 4.0L: 1.3 | 6.3 |
| ThrombocytopeniaG1G2G3G4 | 1.80.800.2 | 6.99.611.22.7 | 1.3000 | 3.85.030.58.8 |
| HemorrhageG1G2G3G4 | 12.32.70.80 | 24.73.71.20.2 | 13.31.32.70 | 36.3000 |
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: Pfizer; Financial Interests, Personal and Institutional, Advisory Board: Pfizer; Financial Interests, Personal and Institutional, Funding, research funding: Pfizer; Financial Interests, Personal and Institutional, Other, clinical trial drug support: Pfizer; Financial Interests, Personal and Institutional, Other, conference/travel support: Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Advisory Board: Eisai; Financial Interests, Personal and Institutional, Other, clinical trial drug support: Eisai; Financial Interests, Personal and Institutional, Funding, research funding: Eisai; Financial Interests, Personal and Institutional, Other, clinical trial drug support: Taiho; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Other, educational grants: AstraZeneca; Financial Interests, Personal and Institutional, Funding, research funding: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: ACT Genomics; Financial Interests, Personal and Institutional, Funding, research funding: ACT Genomics; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Other, educational grant: Roche; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Officer, conference/travel support: MSD; Financial Interests, Personal and Institutional, Other, conference/travel support: Amgen; Financial Interests, Personal and Institutional, Other, clinical trial drug support: Karyopharm; Financial Interests, Personal and Institutional, Other, research funding: Karyopharm. H. Chang: Financial Interests, Personal, Full or part-time Employment: Chang Gung Memorial Hospital; Non-Financial Interests, Personal, Invited Speaker: Chang Gung Memorial Hospital; Non-Financial Interests, Personal, Principal Investigator: Chang Gung Memorial Hospital; Non-Financial Interests, Personal, Advisory Role: Chang Gung Memorial Hospital. H. Macharia: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche. G. Sun: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. F. Lamour: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. D. Oh: Financial Interests, Personal, Advisory Board, Consultant: AstraZeneca; Financial Interests, Personal, Advisory Board, Consultant: Novartis; Financial Interests, Personal, Advisory Board, Consultant: Genentech/Roche; Financial Interests, Personal, Advisory Board, Consultant: Merck Serono; Financial Interests, Personal, Advisory Board, Consultant: Bayer; Financial Interests, Personal, Advisory Board, Consultant: Taiho; Financial Interests, Personal, Advisory Board, Consultant: ASLAN; Financial Interests, Personal, Advisory Board, Consultant: Halozyme; Financial Interests, Personal, Advisory Board, Consultant: Zymeworks; Financial Interests, Personal, Advisory Board, Consultant: BMS/Celgene; Financial Interests, Personal, Advisory Board, Consultant: BeiGene; Financial Interests, Personal, Advisory Board, Consultant: Basilea; Financial Interests, Personal, Advisory Board, Consultant: Turning Point; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Array; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Handok. All other authors have declared no conflicts of interest.