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

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.