273P - A randomized phase II study to determine the efficacy and tolerability of two doses of eribulin plus lapatinib in trastuzumab pre-treated patients...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Breast Cancer
Presenter Joachim Bischoff
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors J. Bischoff1, J. Barinoff2, C. Mundhenke3, D. Bauerschlag4, S.D. Costa5, D. Herr6, K. Lübe7, F. Marmé8, N. Maass9, G. von Minckwitz10, E. Grischke11, V. Müller12, M. Schmidt13, B. Gerber14, S. Kümmel15, C. Schumacher16, P. Krabisch17, M. Thill2, V. Nekljudova18, S. Loibl18
  • 1Frauenklinik, Städtisches Klinikum Dessau, 06847 Dessau-Roßlau - Dessau/DE
  • 2Frauenklinik, Kliniken Markus-Krankenhaus, Agaplesion, Frankfurt am Main/DE
  • 3Universitätsfrauenklinik Kiel, UK-SH, Campus Kiel, Kiel/DE
  • 4Universitätsfrauenklinik Kiel, UK-SH, Campus Kiel, 24105 - Kiel/DE
  • 5Universitätsfrauenklinik Magdeburg, Otto-von Guericke-Universität, Magdeburg/DE
  • 6Frauenklinik, University Hospital Wuerzburg, Würzburg/DE
  • 7Brustzentrum, Henriettenstiftung, Hannover/DE
  • 8Nationales Centrum Für Tumorerkrankungen, University Hospital Heidelberg, Heidelberg/DE
  • 9Frauenklinik, UK-SH, Campus Kiel, Kiel/DE
  • 10Department Of Medical Oncology, German Breast Group, Neu-Isenburg/DE
  • 11Frauenklinik, Universitätsklinikum Tübingen, Tübingen/DE
  • 12Frauenklinik, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, Hamburg/DE
  • 13Frauenklinik, Universitätsmedizin Mainz, Mainz/DE
  • 14Frauenklinik, Universitätsklinikum Rostock, Rostock/DE
  • 15Frauenklinik, Kliniken Essen Mitte Evang. Huyssens-Stiftung, Essen/DE
  • 16Brustzentrum, St. Elisabeth Krankenhaus Hohenlind, Köln/DE
  • 17Frauenklinik, Klinikum Chemnitz gGmbH, Chemnitz/DE
  • 18Medicine And Research, German Breast Group, 63263 - Neu-Isenburg/DE

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

NCT01534455

Legal entity responsible for the study

German Breast Group

Funding

Eisai

Disclosure

G. von Minckwitz: Institution received grant from Eisai. All other authors have declared no conflicts of interest.