A phase II study of the halichondrin B analog, E7389, in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane. A California Consortium/University of Pittsburgh/University of Chicago NCI/CTEP sponsored trial
8056 Background: E7389 is a structurally simplified synthetic macrocyclic ketone analog of halichondrin B and has a unique mechanism of microtubule binding and interaction, distinct from other agents in this class. Thus, it was our hypothesis that pts with prior taxane based therapy would respond to this agent. We conducted a phase II trial of E7389 in prior taxane-treated NSCLC pts. Methods: Eligible pts included: histologically confirmed advanced NSCLC, previous treatment with platinum-based therapy and a taxane, no more than 2 prior regimens, measurable disease, Zubrod performance status ≤ 2. Pts were classified by taxane-sensitivity status: taxane sensitive (TS) (progression >90 days after taxane) or taxane resistant (TR) (progression during or ≤90 days after taxane). Treatment: E7389 1.4 mg/m2 intravenously over 1–2 minutes on day 1 and 8 of a 21 day schedule until disease progression or unacceptable toxicity. Results: 41 pts were entered. There were 3 (15%) objective responses (7.2+, 8.5+, 10.6 mo) of 20 TS pts; and no response of 21 TR pts. Stable disease rate was 60% and 24% in TS and TR pts. respectively. Median progression free survival (PFS) is 6.3 mos TS pts. 95%CI (2.5–8.6 mos) and 1.2 mos TR pts. 95%CI (1.1–4.1 mos). Median number of cycles (range): TS 4 (1–14); TR 2 (1–7). Major toxicity included: 19 pts (46%) with grade 3 or 4 hematologic toxicity including only 1 episode of febrile neutropenia and 8 pts (20%) with grade 3 or 4 non-hematologic toxicity attributable to drug including: fatigue (1), dehydration (2), nausea (2), constipation (2). Only 1 pt developed grade 3 neuropathy (course 9). Conclusions: E7389 was well tolerated with encouraging objective response, PFS and disease control rate in the TS cohort. This cohort will be expanded, using a 2-stage design, to accrue up to another 25 pts. No significant financial relationships to disclose.