Abstract
Capecitabine is frequently used in the treatment of recurrent/progressive metastatic breast cancer (MBC) after prior anthracycline and taxane therapy. With the intention of improving the efficacy of single agent capecitabine, we initiated a randomized, double-blind, placebo-controlled Phase II study of the novel serine/threonine kinase inhibitor enzastaurin in combination with capecitabine in a heavily pretreated patient population. Patients received capecitabine 1,250 mg/m2 twice daily plus enzastaurin 500 mg/day, or capecitabine plus placebo. The capecitabine was administered for the first 14 days of each 21 day cycle. The primary outcome was progression-free survival (PFS) using the log-rank test (1-sided significance level of 0.20). Of 109 patients assessed for eligibility, 85 were enrolled, randomized, and treated (42 and 43 patients in each respective treatment group). The study was terminated early following a preplanned futility analysis. Median PFS (95% CI) was 2.8 (2.1–4.6) months with capecitabine plus enzastaurin versus 4.3 (2.9–6.2) months with capecitabine plus placebo (adjusted hazard ratio: 1.728 [1.00–2.97]; P = 0.048). Median overall survival (95% CI) was lower with capecitabine plus enzastaurin than with capecitabine plus placebo (9.9 [7.0–16.6] months vs 14.9 [9.9–19.3] months, P = 0.181). Grade 3/4 adverse events were more frequent with capecitabine plus enzastaurin (42.9% vs 32.6%). Given the lack of PFS benefit, capecitabine plus enzastaurin is unsuitable as therapy for patients with recurrent/progressive MBC after prior anthracycline and taxane therapy. This trial is registered on www.clinicaltrials.gov (identifier: NCT00437294).
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Acknowledgments
Study sponsorship was provided by Eli Lilly and Company. We thank Jo Wood (Meditech Media Asia Pacific Pty Ltd) for provision of medical writing support. The contributions of all of the investigators, assistants, and patients that participated in this study are also gratefully acknowledged.
Conflict of interest
Mark Clemons and Karen Gelmon have served on advisory boards for Roche. Anil A. Joy has previously served on advisory boards for and has received honoraria from Roche and Eli Lilly (neither of which pertained to the therapeutic agents and/or conduct of this trial). Neill Iscoe is an employee and shareholder of Eli Lilly and Company. Radhi Abdulnabi, Johan P. Jordaan, Mauricio Kotliar, and Jodi Lynch have no conflicts of interest to disclose.
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Clemons, M., Joy, A.A., Abdulnabi, R. et al. Phase II, double-blind, randomized trial of capecitabine plus enzastaurin versus capecitabine plus placebo in patients with metastatic or recurrent breast cancer after prior anthracycline and taxane therapy. Breast Cancer Res Treat 124, 177–186 (2010). https://doi.org/10.1007/s10549-010-1152-0
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DOI: https://doi.org/10.1007/s10549-010-1152-0