A network comparison on efficacy and safety profiling of PD-1/PD-L1 inhibitors in first-line treatment of advanced non-small cell lung cancer

Objective: PD-1/PD-L1 inhibitors are novel immunotherapeutic agents that have been approved for first-line treatment in advanced non-small cell lung cancer (NSCLC). This study aims to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors, which have completed phase 3 clinical trials, as a first-line treatment in patients with advanced NSCLC.

Materials and methods: A systematic search of PubMed, Embase and the Cochrane Library was performed to extract eligible literature up to October 2023. Findings included overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and grade ≥3 treatment-related adverse events (TRAEs). Furthermore, subgroup analyses were conducted based on PD-L1 expression levels and histological type.

Results: We analyzed 29 studies including 18,885 patients. In analyses of all patients, penpulimab plus chemotherapy led the way for OS (HR 0.55, 95% CI: 0.40-0.75) and PFS (HR 0.43, 95% CI: 0.27-0.67). Regarding OS, for patients with PD-L1 expression ≥50%, 1%-49% and <1%, camrelizumab + chemotherapy (HR 0.48, 95% CI: 0.21-1.11), cemiplimab + chemotherapy (HR 0.50, 95% CI: 0.32-0.79) and nivolumab + ipilimumab (HR 0.64, 95% CI: 0.51-0.81) were considered optimal treatments. Compared with chemotherapy, monotherapy with nivolumab, cemiplimab, pembrolizumab, atezolizumab and durvalumab had lower odds of TRAE grade ≥3.

Conclusion: In all patients, penpulimab plus chemotherapy was the most effective therapy, but treatment preferences varied by PD-L1 expression, histology type and associated outcomes. Safety at the individual patient level must be a high priority in the decision-making process. Further validation is warranted.