Safety of PD-L1 inhibitors versus PD-1 inhibitors in the treatment of lung cancer: a systematic review and network meta-analysis

To explore the safety of PD-L1 inhibitors vs. PD-1 inhibitors in extensive-stage small-cell lung cancer (ES-SCLC) and non-small-cell lung cancer (NSCLC). PubMed, EMBASE, and the Cochrane Library were searched up to 20 December 2023. Randomized controlled trials on patients with NSCLC/ES-SCLC treated with PD-1/PD-L1 inhibitor were included and synthesized with Bayesian network meta-analysis. This meta-analysis included 58 studies. Regarding grade ≥3 treatment-related adverse events (TRAEs), PD-L1 inhibitors had better safety compared with PD-1 inhibitors when combined with chemotherapy in resectable NSCLC, presenting larger surface under the cumulative ranking (SUCRA) (0.577 vs. 0.168), similar with those in advanced NSCLC and ES-SCLC. The safety of PD-L1 inhibitors was better than PD-1 inhibitors regarding grade ≥3 pneumonia in resectable NSCLC when combined with chemotherapy (0.648 vs. 0.307), as well as in advanced NSCLC and ES-SCLC. When combined with chemotherapy, PD-L1 inhibitors had better safety regarding grade ≥3 pneumonitis, compared to PD-1 inhibitor (resectable NSCLC: 0.934 vs. 0.019; advanced NSCLC: 0.618 vs. 0.584; ES-SCLC: 0.505 vs 0.059). PD-L1 inhibitors might be a safer option than PD-1 inhibitors regarding grade ≥3 TRAEs and pneumonia, monotherapy or combined with chemotherapy, and when combined with chemotherapy regarding grade ≥3 pneumonitis. PROSPERO (CRD42024620372).