Abstract P4-14-01: Trastuzumab emtansine improves overall survival versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer: Final results from the phase 3 EMILIA study
Authors: Diéras V , Miles D , Verma S , Pegram M , Welslau M , Baselga J , Krop I , Blackwell K , Kang B , Xu J , Green M , Gianni L 
Published: May 2016

Abstract
Introduction
T-DM1 is indicated for the treatment of advanced HER2-positive MBC in patients who previously received trastuzumab and a taxane (separately or in combination) based on data from the phase 3 EMILIA study (BO21977/TDM4370g; NCT00829166). In the primary PFS and second interim OS analyses, respectively, T-DM1 significantly improved PFS (median 9.6 vs 6.4 months; HR=0.65; 95% CI, 0.55–0.77; p&lt;0.0001) and OS (median 30.9 vs 25.1 months; HR=0.68; 95% CI, 0.55–0.85; p&lt;0.0006) compared with capecitabine (X) plus lapatinib (L). T-DM1 treatment was associated with fewer grade ≥3 AEs (41% vs 57%) vs XL. Here we present the final OS analysis from EMILIA.
Methods
EMILIA was a randomized, open-label study of patients with centrally confirmed HER2-positive (IHC3+ and/or FISH amplification ratio ≥2.0), unresectable, locally advanced or MBC, previously treated with trastuzumab and a taxane. Patients were randomized 1:1 to T-DM1 (3.6 mg/kg IV every 3 weeks) or X (1000 mg/m2 PO twice daily, days 1–14 every 3 weeks) plus L (1250 mg PO daily). The final OS analysis was to be conducted following 632 events, and these results are descriptive only. Since the OS efficacy boundary (HR&lt;0.71, p=0.0025) was crossed in the second interim analysis, a protocol amendment allowed crossover from XL to T-DM1.
Results
From Feb 2009 to Oct 2011, 991 patients were randomized to T-DM1 (n=495) or XL (n=496). Patient disposition by the data cutoff (31 Dec 2014) is shown in Table 1. OS was longer with T-DM1 vs XL (median OS 29.9 vs 25.9 months; HR=0.75; 95% CI, 0.64–0.88; p=0.0003). In a sensitivity analysis, which censored crossover patients at the time of switching from XL to T-DM1, the HR was 0.69 (95% CI, 0.59–0.82; p&lt;0.0001). The overall safety profile was similar to previous analyses (Table 2). More grade ≥3 thrombocytopenia occurred with T-DM1 vs XL (14.3% vs 0.4%). Cardiac dysfunction occurred in 2.7% of T-DM1 patients vs 3.5% of XL patients.
Table 1. Patient disposition. T-DM1 (n=495)XL (n=496)Median treatment duration, months7.6X: 5.3 L: 5.5Median duration of follow-up, months47.841.9Discontinued study, n (%)364 (74)404 (82)Crossover, n (%) Per protocolaNot applicable136 (27)Non-protocol therapybX: 252 (54)X: 53 (11) L: 224 (48)L: 74 (15)aMedian duration of follow-up among per-protocol crossover patients was 24.1 months.bBy investigator choice after study treatment discontinuation; X or L could be given in combination with each other or other agents after progression.
Table 2. Safety summary in patients who received ≥1 dose of study treatment.n (%)T-DM1 (n=490)XL (n=488)Grade ≥3 AEs233 (47.6)291 (59.6)Serious AEs91 (18.6)99 (20.3)AEs leading to dose reduction91 (18.6)X: 205 (42.0) L: 98 (20.1)
Conclusions
This final analysis of EMILIA shows an OS benefit of T-DM1 compared with XL. While median drug exposure was longer with T-DM1 than XL, T-DM1 was associated with fewer grade ≥3 AEs and AEs leading to dose reduction compared with XL. These final OS results confirm that T-DM1 treatment improved survival, even in the presence of treatment crossover, and reaffirm T-DM1 as the standard of care in patients with previously treated HER2-positive MBC.
Citation Format: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop I, Blackwell K, Kang B, Xu J, Green M, Gianni L. Trastuzumab emtansine improves overall survival versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer: Final results from the phase 3 EMILIA study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-01.