Efficacy of First-Line Nivolumab Plus Chemotherapy in Advanced Gastric Cancer Stratified by PD-L1 Expression: A Real-World Comparison

<b>Background:</b> Nivolumab plus chemotherapy has shown significant benefits in advanced gastric cancer (AGC) patients with PD-L1 combined positive score (CPS) 5 or higher. However, real-world data on its efficacy across different PD-L1 expression levels are limited. <b>Methods:</b> We conducted a retrospective analysis of 143 AGC patients treated with first-line nivolumab plus chemotherapy. Patients were stratified by PD-L1 CPS. Progression-free survival (PFS), overall survival (OS), and clinical factors affecting outcomes were evaluated. <b>Results:</b> Among 143 patients, 87 (60.8%) were classified as PD-L1 CPS < 5 and 56 (39.2%) as CPS ≥ 5. The PD-L1 ≥ 5 group had a higher proportion of dMMR and TMB-high. Notably, patients in the PD-L1 < 5 group also derived a PFS benefit from chemotherapy plus nivolumab, achieving a median PFS of 6.8 months, although outcomes were further enhanced in the PD-L1 ≥ 5 group with statistical significance (10.0 months; HR 0.56, <i>p</i> = 0.004). Although the PD-L1 ≥ 5 group showed a higher median OS compared with the PD-L1 < 5 group (26.2 vs. 18.8 months), the difference was not statistically significant (<i>p</i> = 0.234). Exploratory analyses demonstrated a stepwise trend toward improved survival with increasing PD-L1 cutoffs, with the most pronounced benefit observed in the PD-L1 ≥ 25 subgroup (PFS HR 0.28, <i>p</i> = 0.012; OS HR 0.21, <i>p</i> = 0.031). <b>Conclusions:</b> This real-world study suggests that nivolumab plus chemotherapy may benefit AGC patients across various PD-L1 expression levels, with trends favoring higher expression. These findings warrant further investigation in larger real-world studies to optimize patient selection and treatment strategies.