title: The Efficacy and Safety of Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors for Advanced Melanoma: A Meta-Analysis of Clinical Trials Following the PRISMA Guidelines.
abstract: The purpose of this study was to investigate the efficacy and safety of programmed cell death 1 (PD-1) and programmed cell death 1 ligand (PD-L1) inhibitors using a meta-analysis of present trials for advanced melanoma. A fully recursive literature search of the primary electronic databases for available trials was performed. The objective response rate (ORR) and the median progression-free survival (PFS) of clinical responses were considered the main endpoints to evaluate the efficacy, whereas Grade 3-4 adverse effects (AEs) were analyzed to evaluate safety. The ORR of PD-1 and PD-L1 inhibitors was 30% (95% CI: 25-35%). No significant difference in the ORR was observed after the comparisons of low-dose, median-dose, and high-dose cohorts. In addition, the rate of Grade 3-4 AEs was 9% (95% CI: 6-12%). According to the 3 randomized controlled trials that compared PD-1 inhibitors with chemotherapy, the difference between these 2 groups was found to be statistically significant with respect to the ORR, PFS and the incidence of Grade 3-4 AEs; that is, the relative risk (RR) of the ORR was 3.42 (95% CI: 2.49-4.69, P < 0.001), the hazard ratio (HR) of the PFS was 0.50 (95% CI: 0.44-0.58, P < 0.001), and the RR of Grade 3-4 AEs was 0.45 (95% CI: 0.31-0.65, P < 0.001). According to a meta-analysis of limited concurrent studies, PD-1 and PD-L1 inhibitors appear to be associated with improved response rates, superior response durability and tolerable toxicity in patients with advanced melanoma.
authors.affiliation: From the Department of Medical Oncology (XG, FM, ZY, BX), and State Key Laboratory of Molecular Oncology (HW, HQ), Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Guan
authors.forename: Haijuan
authors.initials: H
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.forename: Haili
authors.initials: H
authors.lastname: Qian
authors.forename: Zongbi
authors.initials: Z
authors.lastname: Yi
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C585832:pidilizumab; C582435:pembrolizumab