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Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial.
- Source :
-
Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2017 May 01; Vol. 28 (5), pp. 1078-1083. - Publication Year :
- 2017
-
Abstract
- 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.<br />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/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.<br />Results: 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; 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].<br />Conclusions: 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.<br /> (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Carcinoma, Non-Small-Cell Lung pathology
Disease-Free Survival
Double-Blind Method
Female
Humans
Indazoles
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Protein Kinase Inhibitors adverse effects
Pyrimidines adverse effects
Sulfonamides adverse effects
Carcinoma, Non-Small-Cell Lung drug therapy
Dose-Response Relationship, Drug
Protein Kinase Inhibitors administration & dosage
Pyrimidines administration & dosage
Sulfonamides administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1569-8041
- Volume :
- 28
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Annals of oncology : official journal of the European Society for Medical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 28327934
- Full Text :
- https://doi.org/10.1093/annonc/mdx070