Literature DB >> 25691671

Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study.

Miguel Martín1, Sibylle Loibl2, Gunter von Minckwitz2, Serafín Morales2, Noelia Martinez2, Angel Guerrero2, Antonio Anton2, Bahriye Aktas2, Winfried Schoenegg2, Montserrat Muñoz2, José Ángel Garcia-Saenz2, Miguel Gil2, Manuel Ramos2, Mireia Margeli2, Eva Carrasco2, Cornelia Liedtke2, Grischa Wachsmann2, Keyur Mehta2, Juan R De la Haba-Rodriguez2.   

Abstract

PURPOSE: To test whether combining bevacizumab, an anti-vascular endothelial growth factor treatment, with endocrine therapy (ET) could potentially delay the emergence of resistance to ET. PATIENTS AND METHODS: A multicenter, randomized, open-label, phase III, binational (Spain and Germany) study added bevacizumab (15 mg/kg every 3 weeks) to ET (ET-B; letrozole or fulvestrant) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 (HER2) -negative and hormone receptor-positive advanced breast cancer. We compared progression-free survival (PFS), overall survival (OS), overall response rate (ORR), response duration (RD), time to treatment failure (TTF), clinical benefit rate (CBR), and safety.
RESULTS: From 380 patients recruited (2007 to 2011), 374 were analyzed by intent to-treat (184 patients on ET and 190 patients on ET-B). Median age was 65 years, 270 patients (72%) had Eastern Cooperative Oncology Group performance status of 0, 178 patients (48%) had visceral metastases, and 171 patients (46%) and 195 patients (52%) had received prior chemotherapy or ET, respectively. Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.06; P = .126). ORR, CBR, and RD with ET versus ET-B were 22% versus 41% (P < .001), 67% versus 77% (P = .041), and 13.3 months versus 17.6 months (P = .434), respectively. TTF and OS were comparable in both arms. Grade 3 to 4 hypertension, aminotransferase elevation, and proteinuria were significantly higher in the ET-B arm. Eight patients (4.2%) receiving ET-B died during study or within 30 days of end of treatment.
CONCLUSION: The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer.
© 2015 by American Society of Clinical Oncology.

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Year:  2015        PMID: 25691671     DOI: 10.1200/JCO.2014.57.2388

Source DB:  PubMed          Journal:  J Clin Oncol        ISSN: 0732-183X            Impact factor:   44.544


  42 in total

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