Vandetanib Superior to Placebo in Progression-Free Survival in NSCLC; No Benefit in Overall Survival

CHICAGO—Vandetanib maintenance therapy demonstrated longer progression-free survival rates in patients with recurrent non-small cell lung cancer (NSCLC) compared to those receiving placebo as reported by Joseph Aisner, MD, of the Cancer Institute of New Jersey, New Brunswick, and colleagues at the American Society of Clinical Oncology’s 2011 Annual Meeting.

The primary endpoint of the randomized, placebo-controlled Phase 2 trial was progression-free survival (PFS). Overall survival (OS) rates were also evaluated. According to Dr. Aisner, the study was designed to show an improvement in PFS to a median of 6.2 months with the addition of vandetanib maintenance therapy compared to 4.5 months with docetaxel and carboplatin alone.

Patients with advanced non-small cell lung cancer (NSCLC) were randomized to induction therapy with docetaxel (75mg/m2 IV) + carboplatin (AUC=6mg/mL/min IV) on Day 1 of a 21-day cycle and daily vandetanib (100mg/day orally) for four cycles, followed by daily vandetanib (300mg/day orally) or placebo until disease progression. Of the 162 patients randomized to receive induction therapy, 158 actually started induction therapy for a median of 3 cycles (range, 1–4), and 58 patients began maintenance therapy with vandetanib for a median of 3.5 cycles (range, 1–22).

Median age of the study population was 63, 91% had Stage IV/recurrent disease and 52% were male. Neither arm showed significant improvement over historical median PFS of 4.5 months. With median follow-up of 13.5 months, median PFS for patients randomized to maintenance vandetanib was 4.5 months [95% CI, 3.3–5.8]; median PFS for patients randomized to maintenance placebo was 4.2 months [95% CI, 2.8–4.9, stratified log rank P=0.07]. Prolonged PFS for vandetanib maintenance was shown in a multivariate model adjusting for stage (P=0.02). Median OS among patients randomized to maintenance vandetanib was 9.8 months [95% CI, 7.3–15.7], and 9.4 months [95% CI, 7.5–12.2, stratified log rank P=0.68] for patients randomized to maintenance placebo therapy.

The most common toxicities reported during the maintenance phase for vandetanib included rash (n=5), itching (n=3), diarrhea (n=3), dyspnea (n=3), fatigue (n=2), and hypertension (n=2). Eleven deaths were reported due to progressive disease.

Dr. Aisner et al concluded that while neither arm was superior to the historical control of 4.5 months, patients randomized to vandetanib maintenance therapy had longer PFS but not OS compared to placebo.