Activity of eribulin mesylate (E7389) in patients with soft tissue sarcoma (STS): Phase II studies of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC 62052).

Abstract

10031 Background: Eribulin is a synthetic analogue of halichondrin B derived from marine sponges. It inhibits microtubule dynamics via a novel mechanism that is distinct from that of other tubulin-targeting agents, and induces cell cycle arrest and tumor regression in preclinical models. EORTC 62052 assessed the efficacy and safety of eribulin mesylate in 4 independent strata of pts with STS: leiomyo- (LMS,39 pts), adipocytic (ADI,38), synovial (SYN,19) and other (OTH,32) sarcomas. Methods: Pts with intermediate or high grade STS who had received no more than 2 lines of previous chemotherapy (up to 2 single agents or 1 combination) for advanced disease, with documented progression, good performance status and organ function were eligible. Eribulin 1.4 mg/m2 was given i.v. over 2-5 min days 1 and 8 q3w until intolerance or progression. The primary end point was the progression-free rate at 12 wks (PFR12wks) according to RECIST. Secondary end points included safety, response and survival. A Simon 2-stage design was applied (P1: 40%; P0: 20%; α=β=0.1) per stratum. Histopathology and responses were reviewed. Results: Grade 3-4 drug-related AEs occurring in >1 pat were leucopenia (33% of pts), neutropenia (50%), anemia (9%), fatigue (4%), febrile neutropenia, increases in ALAT, and infection without neutropenia (3% each). The PFR12wks was 32% (12/37 evaluable pts) in LMS, 45% (15/33) in ADI, 21% (4/19) in SYN and 19% (5/26) in OTH. The median PFS in LMS was 3 mo (95% confidence interval [CI] 2-5), the median OS 20 (CI 14-N) mo, with 70% of pts alive at 1 year. The PFS in ADI was 3 (CI 2-6) mo, the OS 10 (CI 8-16) mo, with 48% alive at 1 year. The PFS in SYN was 3 (CI 2-3) mo, the OS 11 (CI 7-15) mo, with 36% alive at 1 year. The PFS in OTH was 2 (CI 1- 3) mo, the OS 6 (CI 5-15) mo, with 30% alive at 1 year. Responses included CR, PR and stable disease. Conclusions: Eribulin mesylate is well tolerated in pretreated pts with STS. It deserves further study in well-defined subtypes of sarcoma, as the PFR12wks reached predefined statistical boundaries by the Simon 2-stage design in LMS and ADI. Responses and patient benefit were observed in various histotypes. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai AAIrm, Novartis