Combined Inhibition of EGFR and VEGF Pathways in Patients with EGFR-Mutated Non-Small Cell Lung Cancer: A Systematic Rev
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LUNG CANCER (H BORGHAEI, SECTION EDITOR)
Combined Inhibition of EGFR and VEGF Pathways in Patients with EGFR-Mutated Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis Monica Peravali 1 & Haijun Wang 2 & Chul Kim 1 & Irina Veytsman 1 Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways could potentiate improved outcomes in patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). The purpose of this systematic review and meta-analysis was to compare the efficacy of an EGFR tyrosine kinase inhibitor (TKI) plus a VEGF inhibitor with EGFR TKI alone for the treatment of EGFR-mutated NSCLC. Recent Findings We systematically searched for randomized controlled trials (RCT) that involved patients with EGFR-mutated metastatic NSCLC treated with combination therapy versus EGFR TKI alone. In a pooled analysis of 5 studies, treatment with the combination therapy was associated with statistically significant improvements in progression-free survival (hazard ratio [HR] 0.63, 95% CI [0.54, 0.75]) when compared with control. However, pooled data from 4 studies revealed no statistically significant differences between the 2 groups for overall survival (HR 1.00, 95% CI [0.68, 1.52]) and the objective response rate (relative risk [RR] 1.05, 95% CI [0.97, 1.14]). Summary In patients with metastatic EGFR-mutated NSCLC, treatment with EGFR TKI plus VEGF inhibition provided significant improvements in progression-free survival, but not in overall survival or objective response rate, when compared with treatment with EGFR TKI alone. Keywords EGFR . VEGF inhibition . Anti-angiogenesis . NSCLC . Combination treatment
Introduction
This article is part of the Topical Collection on Lung Cancer * Irina Veytsman [email protected] Monica Peravali [email protected] Haijun Wang [email protected] Chul Kim [email protected] 1
Section of Hematology Oncology, Internal Medicine Department, MedStar Georgetown University Medical Center/Washington Hospital Center, Washington, DC, USA
2
Department of Biostatistics and Biomedical Informatics, MedStar Health Research Institute, Hyattsville, MD, USA
Lung cancer is the second most common malignancy worldwide and a leading cause of cancer-related mortality, comprising 25% of all cancer related deaths [1]. To date, the 5-year relative survival rate for metastatic non-small cell lung cancer (NSCLC) is 6% [1]. The paradigm for management of metastatic NSCLC has improved as a result of advances in immunotherapy, molecular subtyping, and the advent of targeted therapies matched to specific genetic mutations. One of the important molecular targets identified was mutation in the epidermal growth factor receptor (EGFR) pathway. Results from the IPASS randomized controlled trial showed that first-line treatment of metastatic EGFR-mutated NSCLC with an EGFR tyrosin
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