Eribulin mesylate (halichondrin B analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a 2-cohort, phase 2 study

Abstract

Background: Eribulin mesylate is a tubulin inhibitor with activity superior to paclitaxel in NIH:OVCAR-3 human epithelial ovarian cancer xenograft models. In this study, the authors assessed the efficacy of eribulin in platinum-resistant and platinum-sensitive recurrent ovarian cancer.

Methods: Patients with recurrent, measurable epithelial ovarian cancer who had received ≤2 prior cytotoxic regimens and who had adequate organ function were enrolled into 2 separate cohorts: 1) platinum-resistant patients (who had a progression-free interval <6 months after their last platinum-based therapy) and 2) platinum-sensitive patients (who had a progression-free interval ≥6 months after their last platinum-based therapy). Eribulin 1.4 mg/m(2) was administered over 15 minutes intravenously on days 1 and 8 every 21 days. Efficacy was determined by objective response on computed tomography studies.

Results: In the platinum-resistant cohort, 37 patients enrolled, and 36 patients were evaluable for response and toxicity. Two patients achieved a partial response (5.5%), and 16 patients (44%) had stable disease as their best response. The median progression-free survival was 1.8 months (95% confidence interval, 1.4-2.8 months). In the platinum-sensitive cohort, 37 patients enrolled, and all were evaluable for response. Seven patients achieved a partial response (19%). The median progression-free survival was 4.1 months (95% confidence interval, 2.8-5.8 months). The major toxicity was grade 3 or 4 neutropenia (42% of platinum-resistant patients; 54% of platinum-sensitive patients).

Conclusions: Eribulin produced an objective response in 5.5% of women with platinum-resistant, recurrent ovarian cancer and in 19% of women with platinum-sensitive disease. The median progression-free survival was 1.8 months in the platinum-resistant group and 4.1 months in the platinum-sensitive group.

Trial registration: ClinicalTrials.gov NCT00334893.

Copyright © 2011 American Cancer Society.

Figures

Figure 1

Figure 1A. Progression-free survival for the platinum-resistant patient cohort (N=36) Figure 1B. Overall survival for the platinum-resistant patient cohort (N=36)

Figure 1

Figure 1A. Progression-free survival for the platinum-resistant patient cohort (N=36) Figure 1B. Overall survival for the platinum-resistant patient cohort (N=36)

Figure 2

Figure 2A. Progression-free survival for the platinum-sensitive patient cohort (N=37) Figure 2B. Overall survival for platinum-sensitive patient cohort (N=37)

Figure 2

Figure 2A. Progression-free survival for the platinum-sensitive patient cohort (N=37) Figure 2B. Overall survival for platinum-sensitive patient cohort (N=37)