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

作者：Lam S W; de Groot S M; Honkoop A H; Jager A; ten Tije A J; Bos M M E M; Linn S C; van den Bosch J; Kroep J R; Braun J J; van Tinteren H; Boven E^*

来源：European Journal of Cancer, 2014, 50(18): 3077-3088.

DOI：10.1016/j.ejca.2014.10.008

• Metastatic breast cancer
• Phase 2 trial
• Paclitaxel
• Capecitabine
• Bevacizumab

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. %26lt;br%26gt;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. %26lt;br%26gt;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 %26lt; 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 %26lt; 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. %26lt;br%26gt;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.

• 出版日期2014-12