356P - Bevacizumab–Capecitabine (BEV–CAP) After Initial 1st-Line Bevacizumab–Docetaxel (BEV–DOC) in Patients (PTS) With HER2-Negative Metastatic Breast Cancer (MBC): Safety Analysis of the IMELDA Trial

Abstract

ABSTRACT Background Combining BEV with 1st-line chemotherapy (CT) significantly improved progression-free survival (PFS) and response rate (RR) vs CT alone in 3 randomised phase III trials (E2100, AVADO, RIBBON-1). In AVADO, DOC 100 mg/m2 was given for a median of 5.5 months (maximum 9 cycles), after which BEV 15 mg/kg was continued as a single agent. IMELDA was designed in the context of BEV–DOC approval to determine whether efficacy is improved by adding CAP to BEV maintenance therapy after discontinuing DOC. Methods Eligible pts had HER2-negative measurable mBC, ECOG PS 0/1, had received no prior CT for mBC and were eligible for taxane-based CT. After initial 1st-line therapy with 3–6 cycles of BEV–DOC, pts free of progressive disease (PD) were randomised to BEV alone or BEV–CAP (BEV 15 mg/kg q3w; CAP 1000 mg/m2 bid d1–14 q3w) until PD. The primary endpoint is PFS; secondary endpoints include safety, RR and overall survival. Results Between June 2009 and March 2011 (when enrolment to the study was terminated prematurely after withdrawal of BEV–DOC regulatory approval), 284 pts began BEV–DOC. Median age was 52 y (range 24–80), 17% were aged ≥65 y, 53% had ECOG PS 0 and 30% had triple-negative mBC. Maintenance therapy was administered in 183 pts (64%). Key safety results are below. Table: 356P Pts, n (%) Initial BEV–DOC phase (N = 284) Maintenance BEV ± CAP phase (N = 183) Discontinued therapy 99 (35) 134 (73) PD AE Other/unknown 41 (14) 31 (11) 27 (10) 101 (55) 15 (8) 18 (10) Grade ≥3 AEs, n (%) 138 (49) 63 (34) Neutropenia Febrile neutropenia Diarrhoea Mucosal inflammation Asthenia Hand-foot syndrome 44 (15) 30 (11) 3 (1) 9 (3) 6 (2) 6 (2) 2 (1) 0 2 (1) 2 (1) 1 (1) 25 (14) Grade ≥3 BEV AEs of special interest Hypertension Proteinuria Bleeding Arterial TE Venous TE Wound-healing complication GI perforation 5 (2) 1 ( 9 (5) 3 (2) 2 (1) 2 (1) 2 (1) 0 0 AE = adverse event; TE = thromboembolic event Conclusions Most grade ≥3 AEs during BEV–DOC were typical DOC-related AEs. Apart from hypertension and proteinuria, BEV AEs occurred predominantly in early cycles, suggesting that long-term BEV is well tolerated. Efficacy results are expected in 2013. Disclosure J. Gligorov: JG has sat on Advisory Boards and received speaker honoraria from Roche. J. Bines: JB has served on Advisory Boards for Roche. P.A. Cortes: PC has served on Advisory Boards for Roche, BMS and Sanofi-Aventis. U. Freudensprung: UF works as a Contractor for F Hoffmann-La Roche Ltd. G. Mustacchi: GM has acted as a Consultant for Roche, Agendia, Celgene, Novartis, Merck, Glaxo, Eisai. All other authors have declared no conflicts of interest.