Abstract P3-10-07: Phase I trial of eribulin in combination with S-1 for advanced and recurrent breast cancer patients

Abstract

Abstract Introduction: Eribulin is a non-taxane microtubule dynamics inhibitor that has been proved to prolong overall survival in patients with advanced and recurrent breast cancer compared to treatment of physician’s choice. S-1 is an oral fluoropyrimidine anticancer agent that combines tegafur as the effector drug with two modulators, gimeracil, and oteracil potassium, and has shown promising antitumor activity as a single agent for the treatment of advanced breast cancer. In the basis of these results, we aimed to assess the efficacy of the combination of these two drugs in patients with advanced and recurrent breast cancer. In this trial, we determined maximum tolerated dose (MTD) and phase II recommended dose of Eribulin and S-1 combination therapy. Methods: A traditional 3+3 dose escalation design was implemented. 12 patients pre-treated with anthracycline and taxane were enrolled. As an initiation level, patients received s-1 50 mg/m2 from day1 to day14, and Eribulin 1.1mg/m2 on day1, and day8. In level 2, Eribulin dose was increased to 1.4mg/m2. In level 3, S-1 dose was increased to 80 mg/m2. Results: In level 1 or 2, no dose limiting toxicity (DLT) was observed. In level 3, grade 3 hypokalemia occurred in 1 case. The level 3 dose level was determined as phase II recommended dose. Neutropenia was observed in all cases, 3 of which was grade 3 febrile neutropenia. However, other non-hematological toxicity was mild, and the toxicity of the both drugs Safety (N=12)Adverse EventGrade 3/4Leukopenia3 (25%)Neutropenia10 (83%)Febrile Neutropenia3 (25%)Hypokalemia1 (8%) was not enhanced by the combination. Partial response Efficacy (N=12)CR0 (0%)PR5 (41%)SD≥24 weeks2 (17%)SD<24 weeks3 (25%)PD2 (17%)Clinical Benefit7 (58%)Disease Control Rate10 (83%) is confirmed in 5/11 patients with measurable lesions. Conclusion: We have shown that treatment with Eribulin and S-1 is active and well tolerated in patients with advanced and recurrent breast cancer, suggesting that this combination therapy may have potential as a new treatment option. A phase II study is being conducted to evaluate the efficacy and safety. Citation Format: Tsutomu Iwasa, Junji Tsurutani, Satomi Nishida, Yoshifumi Komoike, Kazuhiko Nakagawa. Phase I trial of eribulin in combination with S-1 for advanced and recurrent breast cancer patients [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 P3-10-07.