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Clinical and molecular characteristics associated with the efficacy of PD-1/PD-L1 inhibitors for solid tumors: a meta-analysis

Authors Weng YM, Peng M, Hu MX, Yao Y, Song QB

Received 11 March 2018

Accepted for publication 14 June 2018

Published 30 October 2018 Volume 2018:11 Pages 7529—7542


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava

Yi Ming Weng, Min Peng, Meng Xue Hu, Yi Yao, Qi Bin Song

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, People’s Republic of China

Abstract: We conducted a meta-analysis to estimate the impact of different clinical and molecular characteristics on the efficacy of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors. PubMed and Web of Science were searched for related trials. Eleven eligible studies, comprising 5,663 patients, were included in this meta-analysis. We found that the PD-1/PD-L1 inhibitor was associated with a 31% reduction in the risk of death (hazard ratio [HR]=0.69; 95% CI 0.64–0.74; P<0.00001) for patients with melanoma, non-small-cell lung cancer (NSCLC), urothelial carcinoma, head and neck carcinoma, and renal cell carcinoma. In subgroup analyses, all the patients with PD-L1-positive tumors had overall survival (OS) benefits from PD-1/PD-L1 inhibitors regardless of PD-L1 expression level, and a dose–effect relationship between the expression of PD-L1 and OS benefit from PD-1/PD-L1 inhibitors was observed. There was an OS improvement for patients with a smoking history (P<0.00001), but no OS benefit was observed for nonsmokers (P=0.28). In addition, first-line therapy had better OS than second-line or later treatment (P=0.02). No significant improvement of OS was observed (P=0.70) in patients aged ≥75 years. The relative treatment efficacy was similar according to sex (male vs female, P=0.60), performance status (0 vs ≥1, P=0.68), tumor histology (squamous NSCLC vs non-squamous NSCLC vs melanoma vs urothelial carcinoma vs head and neck carcinoma vs renal cell carcinoma, P=0.64), and treatment type (PD-1 inhibitor vs PD-L1 inhibitor, P=0.36). In conclusion, PD-L1-positive tumors, smoking history, and first-line treatment were potential factors for the efficacy of PD-1/PD-L1 inhibitors. Patients with higher PD-L1 expression might achieve greater OS benefits. In addition, sex, performance status, tumor histology, and treatment type could not predict the efficacy of this therapy. In contrast, patients aged >75 years and nonsmokers might not get OS benefits from this treatment. These results may improve treatment strategies and patient selection for PD-1/PD-L1 inhibitors.

Keywords: anti-programmed cell death 1, biomarker, solid tumor, meta-analysis

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