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

Yangyang Xu, Bing Wan, Xi Chen, Ping Zhan, Yuan Zhao, Tianli Zhang, Hongbing Liu, Muhammad Zubair Afzal, Said Dermime, Steven N. Hochwald, Paul Hofman, Hossein Borghaei, Dang Lin, Tangfeng Lv, Yong Song, written on behalf of AME Lung Cancer Collaborative Group


Background: We conducted a meta-analysis to evaluate the efficacy of anti-programmed cell death 1 (PD-1)/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 anti- PD-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, I2=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.