323PD - Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the GEICAM/GBG LEA s...

Date 01 October 2012
Event ESMO Congress 2012
Session Breast cancer, locally advanced and metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Sibylle Loibl
Authors S. Loibl1, J. De La Haba Rodriguez2, G. von Minckwitz3, S. Morales4, C. Crespo5, A. Antón6, E. Carrasco7, B. Aktas8, K. Mehta9, M. Martin Jimenez10
  • 1Medicine And Research, German Breast Group, 63263 - Neu-Isenburg/DE
  • 2Medical Oncology Department, Reina Sofía Hospital, Córdoba/ES
  • 3Managing Director, German Breast Group, 63263 - Neu-Isenburg/DE
  • 4Medical Oncology Service, Hospital Arnau de Vilanova, Lleida/ES
  • 5Oncology, H Ramon y Cajal, Madrid/ES
  • 6Oncology, H U Miguel Servet, Zaragoza/ES
  • 7Medical, GEICAM, Madrid/ES
  • 8Frauenklinik, Universitätsklinikum, Essen/DE
  • 9Medicine And Research, German Breast Group, Neu-Isenburg/DE
  • 10Oncology, Instituo de Investigación Sanitaria Gregorio Marañón, Madrid/ES

Abstract

Background

We designed the randomized phase III LEA study of first-line bevacizumab in combination with endocrine therapy, to address the hypothesis that anti-VEGF treatment can prevent resistance to endocrine therapy in patients (pts) with advanced breast cancer sensitive to such treatment.

Methods

A multicentre, binational, randomised, open label, phase III study investigated the addition of Bevacizumab (B) 15mg/kg every 3 weeks to an endocrine therapy (ET) with letrozole or fulvestrant (250mg/4 weeks) as first-line therapy in metastatic breast cancer. Postmenopausal pts with HER2-negative and hormone-receptor-positive breast cancer were eligible. The primary objective was to compare progression-free survival (PFS) in the treatment arms. Secondary objectives were overall survival, time to treatment failure, overall response rate, response duration, clinical benefit rate and safety. The recruitment was completed in September 2011. Efficacy analysis will be triggered after 270 events.

Results

From 11/2007 to 11/2011, 380 pts with ER/PgR+ and HER2-tumours were randomised to ET ± B. 38 patients received fulvestrant. Baseline characteristics were well balanced. Median age was 65 years (38-85). 27% had visceral metastases. 36% patients had a prior AI. 110 pts are still on treatment. So far safety data from 335/380 patients are available. Overall 58 serious adverse events in 46 patients were reported 44 in ET-B of which seven were fatal (thromboembolic event x2, hypertension, heart failure, sudden death, liver failure, cerebellum infarction) but only 2 drug related to bevacizumab by the investigator and 14 in ET arm. The main side effects any grade per patient ET-B vs ET were as follows anemia 76% vs 44%, p < 0.001; fatigue 50%vs 31%, p = 0.001; hemorrhage 19% vs 2%, p < 0.001; hypertension 55% vs 12%, p < 0.001; proteinuria 21%vs 3%, p < 0.001; thrombosis grade 3-4, 2.3%vs 0%, p = 0.057.

Conclusions

LEA is the first study to explore the use of an anti-angiogenic drug in combination with an endocrine treatment. The main side effects are of grade 1-2. Final safety data will be presented at the meeting.

Disclosure

All authors have declared no conflicts of interest.