A double-blind, randomized, prospective, phase II trial of capecitabine (Cap) plus enzastaurin (Enz) versus cap plus placebo in patients (pts) with advanced breast cancer (BrCa) and prior anthracycline and taxane treatment.

Abstract

1054 Background: This international trial studied the efficacy and safety of Cap plus Enz in treating advanced BrCa. Methods: Eligible pts (advanced BrCa, prior anthracycline and taxanes, ≤2 prior chemotherapy regimens and performance status ≤2) were randomized to 1250 mg/m2 Cap (days 1 to 14) and a loading dose of 1125 mg Enz on day 1 of Cycle 1 preceding daily 500 mg Enz (Cap-E) or daily placebo (Cap-P) as continuous oral 21-day cycle treatment. Pts discontinued due to progression, death, or adverse event (AE). Response was assessed before alternate cycles. The primary endpoint, progression-free survival (PFS), was compared between arms using log-rank test. Planned enrollment of 60 pts/study arm provided 80% power to detect a 40% PFS improvement with Cap-E over Cap-P (1-sided type-I error=0.20). Results: Prespecified efficacy and safety conditions were not met in a planned interim analysis and the study was terminated. All data from study enrollment to termination were analyzed. 85 pts were randomized (Cap-E, n=42; Cap-P, n=43; median age, 54.2 years) and received ≥1 study drug dose. There were no statistically significant differences between Cap-E and Cap-P, respectively, in PFS (median [95% CI]=2.8 months [2.1, 4.6] versus 4.3 months [2.9, 6.2]; log-rank p=0.237), overall survival (median [95% CI]=9.9 months [7.0, 16.6] versus 14.9 months [9.9, 19.3); log-rank p=0.181), best overall response (11.9% versus 11.6%; Fisher's Exact p=1.00) or duration of response (median [95% CI]=4.3 months [2.2, 4.3] versus 3.5 months [2.8, N/A]; log-rank p=0.812). More Cap-E than Cap-P pts, respectively, experienced ≥1 drug-related (d-r) Grade 3/4 toxicity (42.9% versus 32.6%), d-r serious AE (16.7% versus 14.0%) and d-r hospitalization (14.3% versus 9.3%). Fewer Cap-E (9.5%) than Cap-P pts (11.6%) discontinued due to d-r AEs. There were 4 study d-r deaths (Cap-E, n=2; Cap-P, n=2) on therapy or within 30 days of study treatment discontinuation. Conclusions: When compared with Cap-P, Cap-E did not improve survival outcomes and increased d-r toxicity. These data do not support use of Cap-E in this patient population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly Lilly Lilly, Roche Lilly