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)

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.

Conflict of interest statement

Disclosure: Dr. Baggstrom has received research funding from the Academic and Community Center Research United, AstraZeneca, CtyRx, and MedImmune outside the submitted work. Dr. Socinski has received research funding from the University of North Carolina, University of Pittsburgh, and Pfizer and has received honoraria from and functioned in a consulting/advisory role for Genentech outside the submitted work. Dr. Stinchcombe had functioned in a consulting/advisory role for Bristol-Myers Squibb, Celgene, Boehringer Ingelheim, ARIAD, and Helsinn Healthcare and received research funding from Genentech, Bristol-Myers Squibb, and EMD Serono outside the submitted work. Dr. Edelman has received research funding from Eli Lilly, Bristol-Myers Squibb, Merck, Endocyte, Genentech, and ARIAD and functioned in a consulting/advisory role for Eli Lilly, Bristol-Myers Squibb, Merck, Endocyte, Genentech, and ARIAD outside the submitted work. Dr. Baker Jr. has functioned in a consulting/advisory role for Boehringer Ingelheim outside the submitted work. Dr. Feliciano has functioned in a consulting/advisory role for AstraZeneca and received research funding from Merck and Genentech outside the submitted work. Dr. Hahn has received honoraria from Cardinal Health and compensation for travel, accommodations, and expenses from Cardinal Health outside the submitted work. Mr. Crawford has functioned in a consulting/advisory role for Merck, Novartis, and Pfizer; received research funding from Amgen, AstraZeneca, Bayer, Clovis, and GTx; and served as a data and safety monitoring board member of Celgene, G1Therapeutics, Janssen, Merrimack, and Roche outside the submitted work. The remaining authors declare no conflict of interest.

Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Kaplan-Meier curves of progression-free survival (A) and overall survival (B) for all patients. Abbreviations: HR, hazard ratio; CI, confidence interval; Ref, reference.

Figure 2

Cox proportional hazard multivariate analysis based on progression-free survival (A) and overall survival (B). Abbreviations: HR, hazard ratio; CI, confidence interval; SQC, squamous cell carcinoma.