Efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis.
OBJECTIVE
Vascular endothelial growth factor signaling pathway plays a crucial role in angiogenesis and has become a promising target for cancer drug development. We aimed to quantify the overall efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer (NSCLC).


METHODS
Electronic databases were searched for randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for NSCLC patients. The extracted data on objective response rates (ORRs), disease control rates (DCRs), progression-free survival (PFS) and overall survival (OS) were pooled. Common adverse events (AEs) were also studied.


RESULTS
A total of 33 RCTs involving 17,396 patients were included. Compared with non-angiogenesis inhibitors, angiogenesis inhibitors resulted in significant improvement in PFS (HR, 0.81; 95 % CI 0.76-0.85; p < 0.001), OS (HR, 0.95; 95 % CI 0.92-0.98; p = 0.004), ORR (RR, 1.54; 95 % CI 1.37-1.73; p < 0.001) and DCR (RR, 1.18; 95 % CI 1.10-1.27; p < 0.001). The AEs associated with angiogenesis inhibitors were generally predictable and manageable.


CONCLUSIONS
Angiogenesis inhibitors were superior to non-angiogenesis inhibitors in terms of ORR, DCR, PFS and OS in advanced NSCLC patients. Further studies are warranted to explore the predictive biomarkers to pick up those who may gain utmost benefit from anti-angiogenic therapy.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.
Shaodong
S
Hong
Min
M
Tan
Shouzheng
S
Wang
Shengyuan
S
Luo
Yue
Y
Chen
Li
L
Zhang
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D016017:Odds Ratio; D010671:Phenylurea Compounds / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D000096662:Ramucirumab
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D007191:Indazoles; D007211:Indoles; D009536:Niacinamide; D010671:Phenylurea Compounds; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; D000077157:Sorafenib; D013449:Sulfonamides; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A; D000096662:Ramucirumab; C467484:VEGFA protein, human; C516667:pazopanib; C500926:cediranib; C452423:vandetanib