Phase Ib extension study of eribulin mesylate in combination with carboplatin in patients with chemotherapy-naive advanced non-small cell lung cancer (NSCLC).

Abstract

e19145 Background: Eribulin mesylate as monotherapy has shown antitumor activity in patients with advanced NSCLC that progressed during or after platinum-based doublet chemotherapy (Spira AI et al. Clin Lung Cancer 2012; 13:31-38.). Following evidence of additive activity with eribulin and carboplatin in lung cancer cell lines, a phase Ib, dose-escalation study determined the maximum tolerated dose and optimum administration sequence of the combination as eribulin mesylate 1.1 mg/m2 (0.97 mg/m2 eribulin as free base) followed by carboplatin AUC 6. We report results from an extension arm that investigated the efficacy and safety of this combination in chemo-naïve patients with advanced NSCLC. Methods: Chemo-naïve patients with histologically or cytologically confirmed advanced NSCLC (stage IIIB or IV) with measurable disease were enrolled. Eribulin mesylate was administered intravenously (i.v.) on days 1 and 8 every 21 days, along with carboplatin i.v. on day 1. Efficacy assessments included best overall objective response rate (ORR; RECIST), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR). Adverse events (AEs) were also recorded. Results: 12 patients were accrued (11 male, 1 female) with a median age of 66.5 (range 42-74) years. For the 11 patients evaluable for efficacy, overall ORR was 27.3% (all partial responses) and DCR was 63.6%. Median (range) OS was 12.1 (1.6-12.1) months (5 patients still alive); PFS was 4.2 (0.03+-5.8+) months (upper value censored as 1 patient still responding at final visit); and DOR was 2.9 (2.8-3.1+) months. The most common AEs ≥grade 3 were thrombocytopenia (n=6), neutropenia (n=5), febrile neutropenia (n=4), anemia (n=3), and dyspnea, hypokalemia, leukopenia, and pneumonia (n=2 each). Conclusions: The combination of eribulin and carboplatin yielded no unexpected safety findings. Given the evolving treatment practices for NSCLC, further studies involving larger numbers of patients are warranted, with consideration given to specific histologic subgroups. Clinical trial information: NCT00268905.