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

TL;DR

This study shows that combining nivolumab with chemotherapy can help advanced gastric cancer patients, even those with low PD-L1 levels, though higher PD-L1 levels show better results.

Contribution

The study provides real-world evidence that nivolumab plus chemotherapy benefits gastric cancer patients beyond the standard PD-L1 threshold.

Findings

Patients with PD-L1 CPS ≥ 5 had significantly better progression-free survival than those with CPS < 5.

Even patients with PD-L1 CPS < 5 showed clinically meaningful progression-free survival benefits.

Higher PD-L1 expression levels correlated with better outcomes, especially in the CPS ≥ 25 subgroup.

Abstract

This study evaluated the real-world effectiveness of combining nivolumab with chemotherapy as first-line treatment in 143 patients with advanced HER2-negative gastric cancer. Outcomes were analyzed according to PD-L1 expression. As expected, patients with PD-L1 CPS ≥ 5 showed a significant benefit in progression-free survival compared with those with CPS < 5, while overall survival differences did not reach statistical significance. Importantly, even patients with CPS < 5 demonstrated clinically meaningful benefit, supporting the potential value of this regimen beyond the current CPS ≥ 5 threshold. Exploratory analyses showed a stepwise trend of greater efficacy with increasing PD-L1 expression, most evident in the CPS ≥ 25 subgroup. These findings highlight that nivolumab plus chemotherapy may offer benefit across PD-L1 expression levels and provide practical guidance for treating patients with low PD-L1 expression in real-world clinical settings.

Background: 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. Methods: 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. Results: 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, p = 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 (p = 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, p = 0.012; OS HR 0.21, p = 0.031). Conclusions: 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.

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