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Paclitaxel and bevacizumab with or without capecitabine as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a multicentre, open-label, randomised phase 2 trial
- Source :
- European Journal of Cancer, 50(18), 3077-3088. Pergamon, Lam, S W, de Groot, S M, Honkoop, A H, Jager, A, ten Tije, A J, Bos, M M E M, Linn, S C, Bosch, J, Kroep, J R, Braun, J J, van Tinteren, H & Boven, E 2014, ' Paclitaxel and bevacizumab with or without capecitabine as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: A multicentre, open-label, randomised phase 2 trial ', European Journal of Cancer, vol. 50, no. 18, pp. 3077-3088 . https://doi.org/10.1016/j.ejca.2014.10.008, European Journal of Cancer, 50(18), 3077-3088, European Journal of Cancer, 50(18), 3077-3088. Elsevier Ltd.
- Publication Year :
- 2014
-
Abstract
- Background: The addition of bevacizumab to paclitaxel or capecitabine has demonstrated improved progression-free survival (PFS) and objective response rate (ORR) as compared with chemotherapy alone in patients with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC). We evaluated the efficacy and safety of first-line therapy of paclitaxel and bevacizumab with or without capecitabine in patients with HER2-negative LR/MBC. Methods: In this multicentre, open-label, randomised phase II trial, women with HER2-negative LR/MBC were randomly assigned in a 1: 1 ratio to paclitaxel (90 mg/m(2) intravenously [IV] on days 1, 8, and 15) and bevacizumab (10 mg/kg IV on days 1 and 15) every 4 weeks for six cycles, followed by bevacizumab (15 mg/kg IV on day 1) every 3 weeks (AT) or to paclitaxel (90 mg/m(2) IV on days 1 and 8), bevacizumab (15 mg/kg IV on day 1) and capecitabine (825 mg/m(2) orally twice daily on days 1-14) every 3 weeks for eight cycles, followed by bevacizumab and capecitabine at the same doses every 3 weeks (ATX). The primary end-point was investigator-assessed PFS. Secondary end-points included ORR, duration of response, overall survival (OS) and safety. Exploratory analyses were conducted to evaluate the impact of capecitabine on OS and to validate a novel prognostic model. This trial is registered with EudraCT, number 2006-006058-83. Findings: Median PFS was significantly longer in ATX as compared with AT (11.2 months versus 8.4 months; stratified hazard ratio (HR), 0.52; 95% confidence interval (CI), 0.41-0.67; p < 0.0001). The ORR in ATX patients with measurable disease (n = 268) was higher than that in AT (69% versus 51%; p = 0.01). The median duration of response was 6.8 versus 5.4 months for, respectively, ATX and AT (p < 0.0001). Median OS was 24.2 months for ATX and 23.1 months for AT (p = 0.53). The increased rate of grade 3-4 adverse events related to the addition of capecitabine, being hand-foot syndrome (34% versus 0% for AT) and neutropenia (20% versus 12% for AT), generally did not preclude continuation of treatment. Exploratory analyses indicated that 1) patients receiving capecitabine at some line for treatment have significantly improved OS and 2) a prognostic model can classify patients into three risk groups associated with OS. Interpretation: In patients with HER2-negative LR/MBC, addition of capecitabine to paclitaxel and bevacizumab significantly improved PFS, ORR and response duration. This combination was reasonably well tolerated and may be considered of use as first-line treatment in rapidly progressive disease. (C) 2014 Elsevier Ltd. All rights reserved.
- Subjects :
- Oncology
Adult
Cancer Research
medicine.medical_specialty
Bevacizumab
Paclitaxel
medicine.medical_treatment
Triple Negative Breast Neoplasms
Neutropenia
Antibodies, Monoclonal, Humanized
Deoxycytidine
Capecitabine
chemistry.chemical_compound
SDG 3 - Good Health and Well-being
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Aged
Chemotherapy
business.industry
Hazard ratio
Phase 2 trial
Middle Aged
Metastatic breast cancer
medicine.disease
Treatment Outcome
chemistry
Disease Progression
Female
Fluorouracil
Neoplasm Recurrence, Local
business
Progressive disease
medicine.drug
Subjects
Details
- ISSN :
- 18790852 and 09598049
- Volume :
- 50
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- European journal of cancer (Oxford, England : 1990)
- Accession number :
- edsair.doi.dedup.....6406c36757434c804eaa759e7a8363d2