A randomized double-blind Phase IIa dose-finding study of vandetanib in Japanese patients with NSCLC: PD3-3-2

Copyright © 2007 by the International Association for the Study of Lung Cancer S466 Materials and Methods: Enrollees received Cb AUC 6 day 1 in combination with Pac 100 mg/m2 days 1, 8, and 15 every 4 weeks, and C225 at a loading dose of 400 mg/m2 day 1, then 250 mg/m2 weekly thereafter. C225 was continued as a single agent after 6 full cycles of therapy in patients without disease progression or limiting toxicity. Eligibility stipulated advanced NSCLC (Stage IV, “wet” and IIIB or recurrence after prior surgery/radiation); ECOG performance status 0-1; measurable tumor, and adequate physiologic indices. Results: 53 patients were accrued at FCCC and its OPN partners Amongst the first 32 patients enrolled, 53% were male; median age was 63 years (range 41-86), 47% were PS-0; 6% had received prior RT. Overall response rate was 55% (16/29) including one CR; 3 patients were not evaluable for response: one was found to have brain mets during week 1 and two experienced immediate HSRs. With median potential F/U of ≥ 1 yr, median event-free survival was 5.3 months (n=30) and median survival 11.1 months (n=32). 25% (8/32), received 6 cycles of chemotherapy with 19% (6/32) going onto maintenance C225. Chief grade ≥ 3 attributable adverse events included neutropenia (28%); anemia (6%); HSR (9%) acneiform rash (28%) and hypomagnesemia (19%). Overall inc. (any grade) of rash was 84% and hypomagnesemia 47%. Other significant toxicities included grade 1-2 paronychia, with nail lysis and digital fissures (19%), which tended to be cumulative. Conclusions: C225 in combination with monthly Cb and weekly Pac is highly active in advanced NSCLC. Response and survival data to date are promising. Toxicities match those seen with this PacCb alone, but also include persistent hypomagnesemia, and cumulative paronychia and nail changes, the latter troublesome, if not treatment-limiting. We will report the full results in 9/07.