Purpose: The phase 3 ATTRACTION-2 study demonstrated that nivolumab monotherapy improved survival compared to placebo in patients with pretreated advanced gastric cancer (AGC). However, the efficacy of nivolumab seems to be limited to a subset of patients.
Materials and methods: The predictive values of blood neutrophil-lymphocyte ratio (NLR), serum Na, PD-L1 expression, MSI status, tumor EBV infection, and tumor mutation burden (TMB) were investigated in patients with AGC refractory to ≥2 lines of chemotherapy enrolled from Asan Medical Center in ATTRACTION-2 study.
Results: All 45 patients were analyzed; nivolumab (n = 28) and placebo (n = 17) groups. The objective response rate, median progression-free survival (PFS), and overall survival (OS) were 16.7%, 1.6 months, and 8.1 months in nivolumab group and 0%, 1.6 months and 6.5 months in placebo group. When comparing nivolumab with the placebo group, tumor PD-L1 expression, blood NLR, and serum Na were significant predictive factors of PFS and OS. A multivariate analysis revealed that PD-L1 ( +) and low NLR (≤ 2.9, median) were associated with better PFS. In the nivolumab group, PD-L1 ( +), low NLR, and normal Na (≥ 135 mmol/L) were associated with higher response and disease control rates, while tumor EBV infection and TMB were not.
Conclusion: Tumor PD-L1 expression, blood NLR, and serum Na could be predictive biomarkers for the efficacy of nivolumab in previously treated cases of AGC.
Keywords: Advanced gastric cancer; Nivolumab; Predictive biomarkers; Survival.
© 2022. The Author(s).