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Predicting Nivolumab Efficacy in Advanced Gastric Cancer: Biomarker Analysis

April, 04, 2023 | Gastrointestinal Cancer

KEY TAKEAWAYS

  • The phase 3 ATTRACTION-2 trial tested nivolumab monotherapy in pretreated advanced gastric cancer patients.
  • The primary objective was to determine the predictive values of blood NLR, serum Na, PD-L1 expression, MSI status, tumor EBV infection, and TMB.
  • Nivolumab outperformed the placebo in AGC patients’ overall and progression-free survival. Nivolumab responded better.
  • PD-L1 expression, blood NLR, and serum Na predicted PFS and OS in nivolumab patients.
  • PD-L1 expression, low NLR, and conventional Na were linked with more excellent response and disease control rates in the nivolumab group.

Patients with previously treated advanced gastric cancer (AGC) participated in phase 3 ATTRACTION-2 research, which showed that nivolumab monotherapy enhanced survival relative to placebo. Nevertheless, nivolumab appears to only work for a select group of people. Patients with AGC resistant to ≥ 2 rounds of chemotherapy were enrolled from Asan Medical Center in the ATTRACTION-2 study, and 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 examined.

Researchers enrolled 45 patients, including 28 receiving nivolumab and 17 receiving a placebo. The study reported an objective response rate of 16.7% in the nivolumab group compared to 0% in the placebo group. The median progression-free survival (PFS) was 1.6 months in both groups, while the overall survival (OS) was 8.1 months in the nivolumab group and 6.5 months in the placebo group.

Further analysis of the results showed that tumor PD-L1 expression, blood NLR, and serum Na levels were significant predictive factors for PFS and OS. Multivariate analysis suggested that PD-L1 (+) and low NLR (≤ 2.9, median) were associated with better PFS. In the nivolumab group, patients with PD-L1 (+), low NLR, and normal Na (≥ 135 mmol/L) had higher response and disease control rates. However, tumor EBV infection and TMB did not appear to have a significant impact on treatment response.

Nivolumab as a ≥ 3rd-line therapy in advanced gastric cancer, tumor PD-L1 expression, blood NLR, and serum Na levels could be potential predictive biomarkers for treatment efficacy in previously treated cases of AGC.

Source: https://pubmed.ncbi.nlm.nih.gov/35397540/

Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02267343

Kim JH, Ryu MH, Park YS, Ma J, Lee SY, Kim D, Kang YK. Predictive biomarkers for the efficacy of nivolumab as ≥ 3rd-line therapy in patients with advanced gastric cancer: a subset analysis of ATTRACTION-2 phase III trial. BMC Cancer. 2022 Apr 9;22(1):378. doi: 10.1186/s12885-022-09488-2. PMID: 35397540; PMCID: PMC8994342.

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