Isolating the Role of Bevacizumab in Elderly Patients With Previously Untreated Nonsquamous Non–Small Cell Lung Cancer: Secondary Analyses of the ECOG 4599 and PointBreak Trials

• Authors: Corey J. Langer, University of Pennsylvania; Mark A. Socinski, University of Pittsburgh; Jyoti D. Patel, Northwestern University; Alan B. Sandler, Genentech, Inc.; Joan H. Schiller, University of Texas Southwestern; Larry Leon, Genentech, Inc.; Sebastien Hazard, Genentech, Inc.; Suresh Ramalingam, Emory University
• Journal Title: American Journal of Clinical Oncology
• Volume: Volume 39, Number 5
• Publisher: Lippincott, Williams & Wilkins | 2015-01-24, Pages 441-447
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1097/COC.0000000000000163
• Subjects: Health Sciences, Oncology; Health Sciences, Pharmacology
• Keywords: bevacizumab; chemotherapy; elderly; non–small cell lung cancer

Abstract

Background: Patient-level data from 2 phase III studies in patients with previously untreated, advanced-stage, nonsquamous non–small cell lung cancer (NSCLC) were pooled to examine outcomes with bevacizumab and chemotherapy based on age. Methods: Data from patients randomized to paclitaxel–carboplatin (PC)+bevacizumab in the Eastern Cooperative Oncology Group 4599 (E4599) and PointBreak studies were pooled and compared with E4599 patients randomized to PC alone. Patients were grouped by age: below 65, 65 to 74, 70 to 74, below 75, and 75 years or above. A multivariable model was used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using time-to-event outcomes. Adverse events (AEs) were assessed by age group in each study. Results: The PC+bevacizumab and PC arms comprised 901 and 444 patients, respectively. PC+bevacizumab was associated with significant increases in overall survival relative to PC in patients below 65 years (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.89), 65 to 74 years (HR, 0.80; 95% CI, 0.64-1.00), 70 to 74 years (HR, 0.68; 95% CI, 0.48-0.96), and below 75 years (HR, 0.78; 95% CI, 0.68-0.89) but not in those aged 75 years or above (HR, 1.05; 95% CI, 0.70-1.57). Increased incidence of grade ≥3 AEs was reported with PC+bevacizumab versus PC in patients below 75 years (63% vs. 48%; P<0.05) and 75 years or above (81% vs. 56%; P <0.05) in E4599. Conclusions: This analysis suggests that the survival benefits associated with PC+bevacizumab extend to patient subgroups below 75 years with advanced-stage NSCLC; no benefit, however, was observed for bevacizumab-eligible patients who were 75 years or above.