Maintenance Sunitinib following Initial Platinum-Based Combination Chemotherapy in Advanced-Stage IIIB/IV Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study-CALGB 30607 (Alliance)

J Thorac Oncol. 2017 May;12(5):843-849. doi: 10.1016/j.jtho.2017.01.022. Epub 2017 Feb 1.

Abstract

Introduction: The aim of this study was to evaluate efficacy of maintenance sunitinib after first-line chemotherapy for stage IIIB/IV NSCLC.

Methods: Cancer and Leukemia Group B 30607 trial was a randomized, double-blind, placebo-controlled, phase III study that enrolled patients without progression after four cycles of first-line platinum-based doublet chemotherapy with or without bevacizumab. Bevacizumab was allowed only during the four cycles of chemotherapy. Patients were randomized to receive sunitinib, 37.5 mg/d, or placebo and were treated until unacceptable adverse event(s), progression, or death. The primary end point was progression-free survival (PFS).

Results: A total of 210 patients were enrolled, randomized, and included in the intent-to-treat analysis. Ten patients did not receive maintenance therapy (four who received placebo and six who received sunitinib). Grade 3/4 adverse events affecting more than 5% of the patients were fatigue (25%), thrombocytopenia (12%), hypertension (12%), rash (11%), mucositis (11%), neutropenia (7%), and anemia (6%) for sunitinib and none for placebo. There were three grade 5 events in patients receiving sunitinib (one pulmonary hemorrhage, one other pulmonary event, and one death not associated with a Common Terminology Criteria for Adverse Events term) and two grade 5 events in patients receiving placebo (one other pulmonary event and one thromboembolism). Median PFS was 4.3 months for sunitinib and 2.6 months for placebo (hazard ratio = 0.62, 95% confidence interval: 0.47-0.82, p = 0.0006). Median overall survival was 11.7 months for sunitinib versus 12.1 months for placebo (hazard ratio = 0.98, 95% confidence interval: 0.73-1.31, p = 0.89).

Conclusions: Maintenance sunitinib was safe and improved PFS as maintenance therapy in stage IIIB/IV NSCLC but had no impact on overall survival. There is no room for future investigations of sunitinib in this setting.

Trial registration: ClinicalTrials.gov NCT00693992.

Keywords: Maintenance; NSCLC; Sunitinib; Tyrosine kinase inhibitor.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Eruptions / etiology
  • Fatigue / chemically induced
  • Female
  • Humans
  • Hypertension / chemically induced
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Intention to Treat Analysis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Mucositis / chemically induced
  • Neoplasm Staging
  • Neutropenia / chemically induced
  • Platinum Compounds / administration & dosage
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Quality of Life
  • Sunitinib
  • Survival Rate
  • Thrombocytopenia / chemically induced

Substances

  • Indoles
  • Platinum Compounds
  • Pyrroles
  • Bevacizumab
  • Sunitinib

Associated data

  • ClinicalTrials.gov/NCT00693992