First-line angiogenesis inhibitor plus erlotinib versus erlotinib alone for advanced non-small-cell lung cancer harboring an EGFR mutation

• Published in: Journal of cancer research and clinical oncology 2020-12, Vol.146 (12), p.3333-3339
• Main Authors: Landre, Thierry, Des Guetz, Gaetan, Chouahnia, Kader, Duchemann, Boris, Assié, Jean-Baptiste, Chouaid, Christos
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis inhibitors; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bevacizumab - therapeutic use; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Clinical trials; Enzyme inhibitors; Epidermal growth factor receptors; ErbB Receptors - genetics; Erlotinib Hydrochloride - therapeutic use; Female; Hematology; Humans; Internal Medicine; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Meta-analysis; Middle Aged; Monoclonal antibodies; Mutation; Non-small cell lung carcinoma; Oncology; Original Article – Clinical Oncology; Progression-Free Survival; Protein Kinase Inhibitors - therapeutic use; Small cell lung carcinoma; Targeted cancer therapy; Vascular endothelial growth factor
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-020-03311-w

Purpose Erlotinib is indicated as first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor–receptor ( EGFR ) mutation. Addition of a vascular endothelial growth factor (VEGF) inhibitor (anti-VEGF) in combination with the tyrosine-kinase inhibitor erlotinib in this setting is controversial. Methods We conducted a meta-analysis of randomized trials comparing anti-VEGF plus erlotinib vs erlotinib alone as first-line therapy for advanced NSCLC harboring an EGFR mutation. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and median duration of response (DOR). A fixed-effect model was used. Results Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al.), and another evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients, 654 (53.2%) with exon 19 deletion ( ex19del ) and 568 (46.8%) with EGFR L858R . Patients were predominantly women (63%), Asians (85%) and non-smokers (60%); the median age was 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with prolonged PFS (hazards ratio [HR] 0.59 [95% confidence interval (CI) 0.51–0.69]; p