title: Antiangiogenic Therapy in Advanced Non-small-cell Lung Cancer: A Meta-analysis of Phase III Randomized Trials.
abstract: We conducted a meta-analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non-small-cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the bevacizumab dose. Data of 19,098 patients from 25 phase III trials were analyzed. Compared with the standard of care, the addition of AT did not prolong OS (HR 0.98; 95% confidence interval [CI], 0.96-1.00; P = .1 and HR 0.97; 95% CI, 0.94-1.00; P = .06 for groups 1 and 2, respectively). However, there was a significant improvement in PFS with the addition of AT (HR 0.85; 95% CI, 0.79-0.91; P < .00001 and HR 0.81; 95% CI, 0.75-0.88; P < .00001 for groups 1 and 2, respectively) and overall RR (OR 1.61; 95% CI, 1.30-2.01; P < .0001 and OR 1.72; 95% CI, 1.39-2.14; P < .00001 for groups 1 and 2, respectively). This is the first meta-analysis including only all phase III trials with AT in NSCLC showing no significant effect on OS and an improvement in PFS and RR only. The role of AT in advanced NSCLC is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.
authors.affiliation: Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada. Electronic address: raphaeljack13@hotmail.com.
authors.forename: Jacques
authors.initials: J
authors.lastname: Raphael
authors.affiliation: Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chan
authors.affiliation: Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Safiya
authors.initials: S
authors.lastname: Karim
authors.affiliation: Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Kerbel
authors.affiliation: Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Henry
authors.initials: H
authors.lastname: Lam
authors.affiliation: Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Keemo Delos
authors.initials: KD
authors.lastname: Santos
authors.affiliation: Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Ronak
authors.initials: R
authors.lastname: Saluja
authors.affiliation: Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
authors.forename: Sunil
authors.initials: S
authors.lastname: Verma
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Angiogenesis inhibitors; Lung neoplasm; Response rate; Survival; Systematic review