RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab In Combination with Chemotherapy for Second-Line Treatment of HER2-Negative Metastatic Breast Cancer.

Abstract Background: Three prior Phase III trials (E2100, AVADO, and RIBBON-1) established the clinical benefit of adding bevacizumab (BV) to various chemotherapies (chemos) as first-line treatment for metastatic breast cancer (MBC). A previous Phase III study (AVF2119g) in patients with predominantly heavily pre-treated MBC, in which BV was added to capecitabine (Cape), resulted in a significant increase in objective response rate (ORR), but did not meet the primary endpoint for progression-free survival (PFS). The current study, RIBBON-2, was designed to evaluate the efficacy and safety of the addition of BV to chemotherapies used as second-line treatment for MBC.Methods: Patients were randomized in a 2:1 ratio to chemo+BV or chemo+placebo (PL). Key eligibility criteria included one prior cytotoxic treatment for MBC, ECOG performance status of 0 to 1, and HER2-negative or unknown status. Prior to randomization, investigators chose one of the following chemo agents: taxane (T; paclitaxel 90 mg/m2/wk for 3 of the 4 weeks; paclitaxel 175 mg/m2, nab-paclitaxel 260 mg/m2, docetaxel 75–100 mg/m2, all given q3wk), gemcitabine (G; 1250 mg/m2 on Days 1 and 8 q3wk), Cape (2000 mg/m2 Days 1–14 q3wk), or vinorelbine (V; 30 mg/m2/wk). BV or PL was administered at 10 mg/kg q2wk or 15 mg/kg q3wk, depending on the chemo regimen. The primary endpoint of the study was investigator-assessed PFS pooled across the chemo cohorts. Key secondary endpoints included overall survival (OS), PFS within individual chemo cohorts, ORR, and safety.Results: 684 patients (T, 304; G, 160; Cape, 144; and V, 76) at 211 sites in 19 countries were randomized between February 2006 and June 2008. Overall, the two study arms were balanced for patient characteristics at baseline. The study met its primary endpoint of PFS pooled across chemo cohorts and also demonstrated a 10% increase in ORR when BV was added to chemo. At the interim analysis for OS, the median durations were 18 mo for chemo+BV and 16.4 mo for chemo+PL (see table).Across all chemo cohorts the incidence of BV-related AEs was consistent with data from previous studies. Hypertension was the only BV-related AE consistently increased in the chemo+BV arm across all chemo cohorts.Conclusions: The addition of BV to chemotherapies used for second-line treatment of MBC led to a significant improvement in PFS. The AE profile of BV in the overall study population and across the chemotherapy cohorts was consistent with that previously observed. Additional analyses, including PFS for the individual chemo cohorts, will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 42.