Abstract P3-09-09: Eribulin mesylate plus capecitabine for adjuvant treatment in post-menopausal ER+ early-stage breast cancer: A phase 2, multicenter, open-label study using 2 different dosage regimens
Authors: Smith II John W , Vukelja Svetislava , Hoffman Anthony , Jones Vicky , McIntyre Kristi , Berrak Erhan , Teng Angela , Cox David , O'Shaughnessy Joyce 
Published: May 2015

Abstract
Introduction: Eribulin mesylate is a novel non-taxane microtubule inhibitor. The primary objective of this study was to explore feasibility of administering eribulin plus capecitabine as adjuvant therapy in subjects with early-stage, estrogen receptor-positive (ER+) breast cancer.
Methods: In this phase 2, open-label, multicenter study, 67 postmenopausal women with early HER2-normal/HER2-negative, ER+ breast cancer received four 21-day cycles of treatment with eribulin mesylate (1.4 mg/m2 IV on day 1 and day 8 of each cycle) in combination with capecitabine (900 mg/m2 orally twice daily on days 1 through 14 of each cycle). A second dosage regimen for capecitabine was initiated after dose reductions and treatment discontinuations were noted and attributed to capecitabine-related toxicities, such as grade 3/4 GI events and hand-foot syndrome. As a consequence, capecitabine was administered to an additional cohort of 10 subjects at a fixed dose of 1500 mg given orally twice daily on a 7 days on/7 days off schedule for the 4 cycles; eribulin mesylate was administered on the same dosage schedule as the original regimen (1.4 mg/m2 IV on day 1 and day 8 of each cycle). The 7 days on/7 days off regimen for capecitabine was based on mathematical modeling and has been shown to have an acceptable toxicity profile, including minimal gastrointestinal toxicity, when given in combination with bevacizumab to patients with metastatic breast cancer. Feasibility was assessed based on relative dose intensity (RDI) of the combination using prespecified criteria of 80% of subjects achieving an RDI of at least 85% of the regimen with lower 95% confidence boundary &gt;70%; safety and tolerability were also assessed.
Results: Among subjects on the original eribulin plus capecitabine dosing schedule (n=64), the average (SD) RDI was 90.6% (11.94%) and the feasibility rate was 81.3% (95% lower CI: 71.4%), indicating that this dosage regimen is feasible. Dose reductions, missed doses, and withdrawals due to adverse events were ascribed more to capecitabine (36%, 85%, and 18%, respectively) than to eribulin (21%, 8%, and 12%, respectively), which led to higher RDI and feasibility rates for eribulin (93.5% and 82.8%, respectively) than for capecitabine (87.8% and 71.9%). Grade 3/4 hand-foot syndrome ascribed to capecitabine only, led to dose reductions in 11.9% of subjects under the original dosing schedule. The most common adverse events under the original dosing schedule were alopecia (77.6%), fatigue (58.2%), and nausea (52.2%). With the new dosing schedule (n=9), higher RDI and feasibility rates were achieved, the average RDI was 96% and the feasibility rate was 100%, indicating that this alternative regimen is also feasible, and probably better. (Detailed feasibility and safety data with new dosing regimen will be available at the time of the presentation.)
Conclusions: Adjuvant use of the combination of eribulin plus capecitabine is feasible in patients with early, HER2-normal/HER2-negative, ER+ breast cancer. The combination had an acceptable safety profile under the original dosing schedule and has the potential to be improved by use of a 7 day on/7 day off regimen of capecitabine.
Citation Format: John W Smith II, Svetislava Vukelja, Anthony Hoffman, Vicky Jones, Kristi McIntyre, Erhan Berrak, Angela Teng, David Cox, Joyce O'Shaughnessy. Eribulin mesylate plus capecitabine for adjuvant treatment in post-menopausal ER+ early-stage breast cancer: A phase 2, multicenter, open-label study using 2 different dosage regimens [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-09-09.