Lapatinib (L) in combination with capecitabine has been approved for the treatment of HER2+ advanced breast cancer (ABC) progressed after anthracycline-, taxane-, and trastuzumab (T)-containing therapies. The use is limited by overlapping toxicities. Therefore, other combinations of L with less toxic agents are needed. In the E-VITA study two schedules of Eribulin (E) in association with L have been investigated.
E-VITA (NCT01534455) is a randomized phase II study to determine the efficacy and tolerability of two doses of E plus L in T pre-treated pts with HER2+ ABC. Main eligibility criteria were: ABC not suitable for surgery or radiotherapy alone; adjuvant and up to 3 chemotherapy regimen for ABC. Pts were randomized (1:1) to receive E 1.23mg/m2 iv d1,8 q21 (E1.23) or E 1.76mg/m2 d1 qd21 iv (E1.76) plus L 1000mg os d1-21 (3w cycle). Treatment was given until disease progression or unacceptable toxicity. Primary endpoints were time to progression (TTP), safety and compliance. Secondary endpoints were response rate (RR), clinical benefit rate (CBR) and overall survival (OS). It was planned to recruit a total of 80 pts.
Between 2/2012 and 7/2014 43 pts were randomized (41 started treatment). The study was stopped in 7/2014 due to slow accrual. Median age was 54 yrs. Median TTP was 8.1 months (95% CI 4.8-9.4) with E1.23 vs 6.5 months (95% CI 4.6-13.4) with E1.76. No difference in OS was seen (23.1 [95% CI 12.5-35.0] vs 23.2 months [95%CI 13.7-30.1]). RR was 52.4% (95% CI 31.0-73.7) vs 45.0% (95% CI 23.2-66.8). CBR was 71.4% (95% CI 52.1-90.8) vs 75.0% (56.0-94.0). High grade adverse events (AEs) were more common under E1.76. Overall the most frequently grade 3-4 AEs were neutropenia (47.6% vs 70.0%), fatigue (19.0% vs 0.0%) and diarrhea (9.5% vs 5.0%). 5 pts discontinued therapy due to AEs (2 in E1.23 arm and 3 in E1.76), 13 pts in both arms due to progression.
The combination of E and L show an acceptable safety profile. Due to premature study termination, no definitive conclusion on efficacy can be drawn. However, due to its lower toxicity profile, the preferred regimen remains E1.23 d1,8 q21.
Clinical trial identification
Legal entity responsible for the study
German Breast Group
G. von Minckwitz: Institution received grant from Eisai. All other authors have declared no conflicts of interest.