Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial

<span class="paragraphSection"><div class="boxTitle">Background</div>Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population.<div class="boxTitle">Patients and methods</div>In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed.<div class="boxTitle">Results</div>A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23–55] with P800, increasing to 69% (95% CI 50–84; <span style="font-style:italic;">P</span> = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%–86%) with pazopanib and 83% (95% CI 74%–92%) with placebo [hazard ratio = 1.3 (95% CI 0.6–2.7), <span style="font-style:italic;">P</span> = 0.53]. Five-year overall survival was 83% (95% CI 72–94) with pazopanib and 94% [95% CI 88–100] with placebo [hazard ratio = 1.8 (95% CI 0.6–5.5), <span style="font-style:italic;">P</span> = 0.26].<div class="boxTitle">Conclusions</div>In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.</span>

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