Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial
Mené en France sur 71 patients atteints d'un cancer du poumon non à petites cellules de stade I ayant subi une résection complète, cet essai de phase II/III évalue l'observance à plus de 3 mois, l'efficacité, du point de vue de la survie globale, et la toxicité du pazopanib en traitement adjuvant
Background: 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. Patients and methods: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/d (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/d (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed. Results: 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; p=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], p=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], p=0.26). Conclusions: In resected stage I NSCLC patients adjuvant 400 mg/d pazopanib but not 800 mg/d was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.