The association of PD-L1 expression status and PD-1/PD-L1 inhibitors-related toxicities profile in non-small cell lung cancer

Purpose PD-L1 expression has been explored to guide the treatment options for programmed cell death 1 and its ligand (PD-1/PD-L1) inhibitors-based therapy in non-small cell lung cancer (NSCLC), but the association of its treatments-related toxicities profile with PD-L1 expression status is unclear. To make the optimized and personalized use of such agents, we performed current study. Experimental Design : Multiple databases (Cochrane Library, EMBASE, and PubMed databases) from inception to June 30, 2024 were retrieved to search PD-1/PD-L1 inhibitors-related clinical trials of NSCLC that had described data regarding treatment-related adverse events (TRAEs) and PD-L1 expression. Results Twenty-six trials, involving 5,453 patients, were eligible for final analysis. PD-L1-positive patients suffered a higher frequency of AEs leading to discontinuation, and grade 3–4 treatment-related adverse events (TRAEs) compared with PD-L1-negative patients at most cut-off value. However, the frequency of all-grade TRAEs, SAEs, and FAEs showed numerically difference among PD-L1-positive and PD-L1-negative patients at most cut-off value. Different PD-1/PD-L1 inhibitors type did not detect a consistent dose-dependent pattern between PD-L1-positive and toxicities profile. Subgroup analyses noted that patients using 22C3 immunohistochemistry assay have a higher frequency of all-grade TRAEs. Moreover, patients receiving first-line therapy and those enrolled in open-label trials experienced a higher frequency of grade 3–4 TRAEs. Conclusions We suggested that clinicians, and patients should be informed of the association of PD-L1 expression status and toxicities profile prior to PD-1/PD-L1 inhibitors administration.