Efficacy and safety of PD-L1 versus PD-1 inhibitors as consolidation therapy following concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer: a real-world retrospective study

Abstract

The PACIFIC trial established consolidation immune checkpoint inhibitors (ICIs) following concurrent chemoradiotherapy (cCRT) as standard care for unresectable stage III non-small cell lung cancer (NSCLC). Both programmed cell death protein 1 (PD-1) and programmed death‑ligand 1 (PD-L1) inhibitors are used, but their comparative effectiveness and safety remain uncertain. A single-center retrospective cohort study was conducted to compare survival and treatment-related pneumonitis between PD-1 and PD-L1 inhibitors consolidation therapy in 181 patients with unresectable stage III NSCLC who received ICIs following cCRT (May 2019–May 2024). Primary endpoint was progression-free survival (PFS), and secondary endpoint was overall survival (OS). Survival curves were generated using the Kaplan-Meier method. Exploratory subgroup analysis was used to compare the survival benefit of the two drugs in populations with different clinical characteristics. Cox proportional hazards regression models were employed to identify factors associated with survival outcomes. Competing risk model was used to assess the risk of treatment-related pneumonitis. PD-L1 consolidation was associated with significantly improved PFS compared with PD-1 inhibitors (adjusted HR 0.57, 95% CI 0.37–0.88, P = 0.011; log-rank P = 0.016). However, no statistically significant difference in OS was observed between the two groups (adjusted HR 0.60, 95% CI 0.32–1.11, P = 0.101; log-rank P = 0.052). Exploratory subgroup analysis demonstrated that PD-L1 inhibitors were associated with a lower hazard of disease progression in patients with a smoking history. The cumulative incidence of grade ≥ 2 pneumonitis showed no statistically significant difference between the two groups ( P = 0.795), whereas the incidence of grade ≥ 3 pneumonitis was higher in the PD-L1 group, although this difference did not reach statistical significance ( P = 0.244). For patients with unresectable stage III NSCLC receiving cCRT, consolidation therapy with PD-L1 inhibitors may be associated with prolonged PFS compared with PD-1 inhibitors. Exploratory subgroup analysis suggested a greater benefit in patients with a smoking history. Owing to the limitations of this retrospective analysis, large-scale, multicenter studies with biomarker stratification are needed to optimize immunotherapy strategies.