Vandetanib versus placebo in patients with advanced non-small cell lung cancer (NSCLC) after prior therapy with an EGFR tyrosine kinase inhibitor (TKI): A randomized, double-blind phase III trial (ZEPHYR).

Abstract

7525 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. This study assessed whether vandetanib conferred an overall survival (OS) benefit vs placebo in patients (pts) with locally advanced or metastatic NSCLC after failure of prior therapy with an EGFR TKI. Methods: Eligible pts (stage IIIB/IV NSCLC; WHO PS 0–2; all histologies permitted; 1–2 prior chemotherapies; prior EGFR TKI) were randomized 2:1 to receive vandetanib 300 mg/day or placebo until progression/toxicity. The primary objective was to show superiority in OS (> 90% power to detect ≥ 25% reduction in death rate; hazard ratio [HR] ≤ 0.75). Secondary efficacy endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) at 8 weeks. Results: Between Nov 2006–Nov 2008, 924 pts (mean age 60 yrs; 53% female; 56% East Asian; 53% non-smoker; 79% adenocarcinoma; 58% 2 previous chemotherapy regimens) received vandetanib (n = 617) or placebo (n = 307). Baseline chara...