Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial comparing bevacizumab with or without erlotinib as maintenance therapy for the treatment of Advanced Non-Small-Cell Lung Cancer (ATLAS)
Journal
Journal of Thoracic Oncology
Journal Volume
9
Journal Issue
9
Pages
1411-1417
Date Issued
2014
Author(s)
Kabbinavar F
Fehrenbacher L
Hainsworth J
Kasubhai S
Kressel B
Marsland T
Patel T
Rubin M
White L
Klughammer B
Colburn D
Miller V
Johnson B.E.
Abstract
INTRODUCTION: ATLAS compared bevacizumab plus erlotinib (B+E) with bevacizumab plus placebo (B+P) as maintenance therapy after first-line bevacizumab plus chemotherapy (B+C) for advanced non-small-cell lung cancer (NSCLC). Prespecified biomarkers were prospectively evaluated. METHODS: Tumor samples were analyzed for: epidermal growth factor receptor (EGFR) expression (immunohistochemistry [IHC]); EGFR gene copy number (fluorescence in-situ hybridization [FISH]); EGFR mutations (exon 19 deletions/L858R mutations); and KRAS mutations (exons 2/3). Progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: Of 743 patients randomized to receive maintenance treatment (after four cycles of B+C without progression), 190 (B+E) and 177 (B+P) were evaluable for biomarker status. Median PFS (from randomization) was 4.4 months (B+E) versus 3.7 months (B+P; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.99), which was numerically similar to the intent-to-treat PFS. PFS benefit of B+E was observed across most biomarker subgroups. EGFR IHC, EGFR FISH, and EGFR/KRAS mutation status were not predictive of outcome. B+E-treated patients with EGFR mutation-positive NSCLC had longer PFS compared with B+P-treated patients (HR, 0.44; 95% CI, 0.22-0.86; p = 0.0139). Patients with KRAS wild-type disease had significant PFS improvements with B+E, compared with B+P (HR, 0.66; 95% CI, 0.485-0.914; p = 0.0105). No OS benefit of B+E was observed. CONCLUSIONS: Patients with KRAS wild-type or EGFR mutation-positive NSCLC derived PFS benefits from B+E. However, EGFR IHC, EGFR FISH, and EGFR or KRAS mutation status were not strongly predictive of survival. A larger sample size would be needed to confirm the initial trends observed in this study. Copyright ? 2014 by the International Association for the Study of Lung Cancer.
Subjects
Bevacizumab; Biomarkers; Erlotinib; Maintenance; Non-small-cell lung cancer
SDGs
Other Subjects
bevacizumab; carboplatin; cisplatin; docetaxel; epidermal growth factor receptor; erlotinib; gemcitabine; paclitaxel; placebo; tumor marker; angiogenesis inhibitor; bevacizumab; epidermal growth factor receptor; erlotinib; monoclonal antibody; protein kinase inhibitor; quinazoline derivative; tumor marker; vasculotropin A; adult; advanced cancer; aged; article; cancer combination chemotherapy; cancer radiotherapy; cancer surgery; cancer survival; controlled study; double blind procedure; epidermal growth factor receptor gene; female; fluorescence in situ hybridization; gene dosage; gene mutation; human; immunohistochemistry; intention to treat analysis; large cell carcinoma; lung adenocarcinoma; lung non small cell cancer; lung squamous cell carcinoma; maintenance chemotherapy; major clinical study; male; middle aged; multiple cycle treatment; oncogene; oncogene K ras; outcome assessment; overall survival; patient history of radiotherapy; patient history of surgery; phase 3 clinical trial; prediction; priority journal; progression free survival; protein expression; randomized controlled trial; survival rate; survival time; wild type; young adult; adolescent; antagonists and inhibitors; Carcinoma, Non-Small-Cell Lung; clinical trial; disease free survival; drug combination; epidemiology; Lung Neoplasms; metabolism; mortality; multicenter study; trends; United States; Adolescent; Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Quinazolines; Receptor, Epidermal Growth Factor; Survival Rate; Tumor Markers, Biological; United States; Vascular Endothelial Growth Factor A; Young Adult
Publisher
Lippincott Williams and Wilkins
Type
journal article