A phase II study of halichondrin B analogue eribulin mesylate (E7389) in patients with advanced non-small cell lung cancer previously treated with a taxane: a California Cancer Consortium trial

• Type of Material: Article
• Authors: Barbara J Gitlitz, University of Southern California; Denice D Tsao-Wei, University of Southern California; Susan Groshen, University of Southern California; Angela Davies, University of California at Davis; Marianna Koczywas, City Hope National Medical Center; Chandra P Belani, Penn State Hershey Cancer Institute; Athanassios Argiris, University of Pittsburgh; Suresh S Ramalingam, Emory University; Everett E Vokes, University of Chicago; Martin Edelman, University of Maryland; Philip Hoffman, University of Chicago; Marc S Ballas, New York University; Stephen V Liu, University of Southern California; David R Gandara, University of California at Davis
• Language: English
• Date: 2012-03-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 by the International Association for the Study of Lung Cancer.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/JTO.0b013e31823f43ca
• Title of Journal or Parent Work: Journal of Thoracic Oncology
• ISSN: 1556-0864
• Volume: 7
• Issue: 3
• Start Page: 574
• End Page: 578
• Keywords: DOCETAXEL; Life Sciences & Biomedicine; Respiratory System; Science & Technology; Oncology; Taxane-sensitive; Halichondrin B; Eribulin mesylate; Non-small cell lung cancer; Taxane-refractory; CHEMOTHERAPY
• Research Categories: Health Sciences, General; Health Sciences, Oncology

Abstract

Eribulin mesylate (E7389) is an analog of halichondrin B with a unique mechanism of microtubule binding. The activity and toxicity of eribulin were assessed in patients with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane. Methods: An open-label phase II study included patients with NSCLC previously treated with platinum and taxane-based therapy, with up to two prior cytotoxic regimens, given for metastatic disease or as adjuvant therapy. Patients were stratified by taxane-sensitivity: taxane-sensitive (TS, progression >90 days after taxane) or taxane-resistant (TR, progression ≤90 days after taxane). Patients received an intravenous infusion of eribulin at 1.4 mg/m2on days 1 and 8 every 21 days. The primary end point was objective response rate and secondary end points included progression-free survival and overall survival. Results: Sixty-six patients were accrued. The objective response rate was 5% with a median duration of response of 7.8 months. In the TS arm, 3 of 45 patients (7%) achieved a partial response and another 11 of 45 (24%) achieved stable disease for at least 3 months, whereas in the TR arm, no patients achieved a partial response and 4 of 21 (19%) achieved stable disease for at least 3 months. Median progression-free survival was 2.9 months in the TS subgroup and 1.2 months in the TR subgroup. The median overall survival was 12.6 months in the TS subgroup and 8.9 months in the TR subgroup. Toxicities were primarily hematologic; only two patients developed grade 3 neuropathy. Conclusions: Eribulin mesylate is well tolerated and demonstrates activity in pretreated, TS NSCLC.