The association of PD-L1 expression with the efficacy of antiPD-1/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: a meta-analysis of randomized controlled trials

Background: We conducted a meta-analysis to evaluate the efficacy of anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) monotherapy or immunotherapy combined with chemotherapy and further estimated the value of PD-L1 expression in predicting the response from anti-PD-1/PD-L1 treatments as monotherapy or in combination with chemotherapy. Methods: Clinical trial data were searched from electronic databases, which evaluated PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC) and correlated with PD-L1 expression levels. Results: Fifteen randomized-controlled trials involving 10,074 patients were identified. Comparing antiPD-1/PD-L1 monotherapy to chemotherapy, the pooled HR for overall survival (OS) was 0.77 (95% CI: 0.69-0.85, P<0.00001). Subgroup analyses revealed that patients had longer OS at >= 1%, >= 5%, >= 10% and >= 50% PD-L1 expression levels. Patients with higher PD-L1 expression may get increased benefit from PD-1/PD-L1 inhibitors. Moreover, patients with PD-L1 >= 50% had an objective response rate (ORR) improvement from anti-PD-1/PD-L1 therapy (RR = 1.87, 95% CI: 1.27-2.75, P=0.001), but no ORR benefits were observed in patients with PD-L1 expression <1% (RR = 0.82, 95% CI: 0.56-1.22, P=0.33) or 1-49% (RR = 0.80, 95% CI: 0.64-0.98, P=0.03). OS was significantly better in patients receiving second-orthird line treatments (P<0.00001) with PD-L1 >= 1%. The efficacy of PD-1 inhibitors was similar to that of PD-L1 inhibitors, with no significant difference (P=0.63, I-2=0%). Furthermore, immunotherapy combined with chemotherapy had better OS (HR = 0.64, 95% CI: 0.48-0.84, P=0.001) than chemotherapy alone. Subgroup analyses showed that patients benefited from the combined chemo-IO treatment in the first-line setting regardless of PD-L1 expression level. Conclusions: PD-L1 expression may be a valuable predictor of the efficacy of anti-PD-1/PD-L1 monotherapy in certain NSCLC patients. However, the combination of chemotherapy plus immunotherapy significantly improved survival regardless of the PD-L1 expression level in the first-line treatment of NSCLC.