title: Safety profile of combined therapy inhibiting EFGR and VEGF pathways in patients with advanced non-small-cell lung cancer: A meta-analysis of 15 phase II/III randomized trials.
abstract: The efficacy of combined vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibition in patients with advanced non-small-cell lung cancer (NSCLC) was well studied. However, few studies focused on the risk and adverse events (AEs) of combined targeted therapy. The aim of this meta-analysis was to evaluate the safety profile of combined targeted therapy against EFGR and VEGF in patients with advanced NSCLC. A comprehensive literature search in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts and ESMO Abstracts was conducted. Eligible studies were randomized clinical trials (RCTs) that compared safety profile of combined therapy inhibiting EFGR and VEGF pathways with control groups (placebo, single EGFR or VEGF inhibition therapy, chemotherapy or a combination of them) in patients with advanced NSCLC. The endpoints included treatment discontinuation, treatment-related deaths and AEs. The search identified 15 RCTs involving 6,919 patients. The outcomes showed that three of four pairwise comparisons detected more discontinuation due to AEs in combined targeted therapy, with odds ratio (OR) compared with the control groups ranged from 1.97 to 2.29. Treatment with combined inhibition therapy was associated with several all-grade and grade 3 or 4 AEs (e.g. rash, diarrhea and hypertension). Also, there was a significantly higher incidence of treatment-related deaths in combined inhibition using vandetanib versus single EGFR inhibition therapy (OR = 1.97, 95% CI 1.19-3.28). In conclusion, combined inhibition therapy against EGFR and VEGF in patients with advanced NSCLC was associated with increased toxicity. Increased AEs hinder patient compliance and reduce their quality of life, leading to dose reduction or discontinuation.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Sciences, Biology and Biomedical Sciences, Harvard Medical School, Boston, MA.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jiale
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Rehabilitation, The Second People's Hospital of Huai'an, Huai'an, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Ji
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Qi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017063:Outcome Assessment, Health Care; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D010880:Piperidines; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; C452423:vandetanib
keywords: EGFR; VEGF; adverse events; non-small-cell lung cancer; randomized clinical trial; targeted therapy