A Phase II Study of Eribulin Mesylate (E7389) in Patients With Advanced, Previously Treated Non-Small-Cell Lung Cancer

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death. Eribulin mesylate is a novel non-taxane microtubule dynamics inhibitor that showed anti-tumor activity in phase I studies in NSCLC. This phase II study assessed efficacy and tolerability of eribulin in advanced, previously treated NSCLC. Eribulin was active and tolerated, and represents a potential treatment option for NSCLC. Introduction: This open-label phase II study assessed the efficacy and tolerability of eribulin, a non-taxane microtubule dynamics inhibitor with novel mechanism of action, as monotherapy in patients who have advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Enrolled patients had progressed during or after platinum-based doublet chemotherapy. Initially, two patient cohorts (taxane-pre-treated and taxane-nave) received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. To assess tolerability of a second dosing schedule, a cohort of taxane-pre-treated patients received eribulin on days 1 and 8 of a 21-day cycle. The primary endpoint was objective response rate (ORR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by independent radiographic review. Results: One hundred three patients received eribulin. The ORR was 9.7% (all partial responses [PR]). Overall disease control rate (PR + stable disease) was 55.3%. Median duration of response, progression-free survival, and overall survival were 5.8, 3.4, and 9.4 months, respectively. The most common drug-related adverse events were neutropenia (54%; 49% grade 3/4); fatigue (49%; 11% grade 3, no grade 4); nausea (38%; 1% grade 3, no grade 4); alopecia (32%); anemia (29%, 4% grade 3/4) and neuropathy (23%; 2% grade 3, no grade 4). The 28-day schedule was associated with many dose delays, interruptions, or omissions due to neutropenia (day 15). The 21-day cycle was well-tolerated. Conclusions: Eribulin monotherapy administered on days 1 and 8 of a 21-day cycle is active and tolerated as second-or later-line chemotherapy for NSCLC.