Abstract 346P
Background
Eribulin is approved for the treatment of previously treated metastatic breast cancer (BC) and liposarcoma. E7389-LF is a liposomal formulation of eribulin. Results of the dose-escalation part of a phase I study of E7389-LF have been previously reported and determined that 2.0 mg/m2 tri-weekly (Q3W) is the recommended regimen. The expansion part then assessed the safety and efficacy of this recommended regimen of E7389-LF in pts with advanced HER2-negative BC.
Methods
Eligible BC pts had no standard therapy, had received previous anthracycline- and taxane-based treatments, and ≤3 prior chemotherapy regimens. Target sample size was 27 pts based on Fleming’s 2-stage design. The true response rate of the null hypothesis was 10%, the alternative was 30% with a type I error rate of 5% (one-sided), and a power of 85%. E7389-LF 2.0 mg/m2 was administered intravenously Q3W. Response was assessed Q6W by RECIST v1.1. Toxicity was assessed using CTCAE 4.03.
Results
As of January 2020, 28 pts had been enrolled: Median age was 59 years (range 31-78), 85.7% had ECOG-PS 0, and the median number of prior therapies for metastatic disease (including endocrine therapy) was 3 (range 1-8). Luminal BC was reported in 75.0% of pts and 25.0% had triple-negative BC (TNBC). Objective response rate was 35.7% (95% CI: 18.6-55.9) in all pts; in luminal BC and TNBC pts it was 42.9% (95% CI: 21.8-66.0) and 14.3% (95% CI: 0.4-57.9), respectively. Disease control rate (stable disease + partial or complete response) was 89.3% (95% CI: 71.8-97.7). Median progression-free survival was 7.1 months (95% CI: 3.9-12.2). Common grade ≥3 AEs included neutropenia (67.9%), leukopenia (42.9%), and thrombocytopenia (32.1%). Incidences of febrile neutropenia in cycle 1, with and without prophylactic peg-filgrastim, were 10.0% and 33.3%, respectively. AEs caused discontinuation from the study in 1 pt.
Conclusions
E7389-LF 2.0 mg/m2 Q3W was well tolerated with a manageable safety profile and showed promising antitumor activity in pts with heavily treated, advanced, HER2-negative BC, although neutropenia should be carefully monitored and the use of peg-filgrastim can be considered. The results support further development of E7389-LF in advanced HER2-negative BC.
Clinical trial identification
NCT03207672.
Editorial acknowledgement
Editorial support was provided by Oxford PharmaGenesis, Newtown, PA and was funded by Eisai Inc., Woodcliff Lake, NJ, USA.
Legal entity responsible for the study
Eisai Co., Ltd., Tokyo, Japan.
Funding
Eisai Co., Ltd., Tokyo, Japan.
Disclosure
S. Takahashi: Honoraria (self), Research grant/Funding (self): Eisai; Honoraria (self), Research grant/Funding (self): Ono pharmaceutical; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): Chugai; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self), Research grant/Funding (self): AstraZeneca. T. Mukohara: Research grant/Funding (self): Daiichi-Sankyo; Research grant/Funding (self): Sysmex; Honoraria (self), Research grant/Funding (self), lecture fees: Eisai; Research grant/Funding (self): MSD; Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self), lecture fees: Novartis; Research grant/Funding (self): Sanofi; Honoraria (self), Research grant/Funding (self), lecture fees: Chugai; Honoraria (self), lecture fees: Eli Lilly; Honoraria (self), lecture fees: AstraZeneca; Honoraria (self), lecture fees: Kyowa-Kirin. Y. Naito: Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Taiho; Speaker Bureau/Expert testimony: Nippon Kayaku; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Merck Serono; Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: Meiji Seika; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche Diagnostics; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Chugai Pharmaceutical; Speaker Bureau/Expert testimony: Eisai. T. Suzuki: Full/Part-time employment: Eisai Co., Ltd.. T. Takase: Full/Part-time employment: Eisai Co., Ltd.. R. Matsunaga: Full/Part-time employment: Eisai Co., Ltd.. N. Masuda: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo. All other authors have declared no conflicts of interest.