Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair

Young-Gyu Park; Hyung-Don Kim; Jaewon Hyung; Young Soo Park; Min-Hee Ryu

doi:10.1007/s10120-024-01509-2

Factors associated with the efficacy of first-line nivolumab plus chemotherapy in advanced gastric cancer patients with deficient mismatch repair

Gastric Cancer. 2024 May 23. doi: 10.1007/s10120-024-01509-2. Online ahead of print.

Authors

Young-Gyu Park^{1

2}, Hyung-Don Kim¹, Jaewon Hyung¹, Young Soo Park³, Min-Hee Ryu⁴

Affiliations

¹ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
² Division of Hematology/Oncology, Department of Internal Medicine, Konyang University Hospital, Daejeon, South Korea.
³ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
⁴ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. miniryu@amc.seoul.kr.

PMID: 38780852
DOI: 10.1007/s10120-024-01509-2

Abstract

Background: We aimed to investigate clinicopathologic factors leading to different clinical outcomes in patients with deficient mismatch repair protein (d-MMR) gastric cancer (GC) treated with nivolumab plus chemotherapy (nivolumab chemotherapy).

Methods: This retrospective study included 28 patients with d-MMR advanced GC treated with first-line nivolumab chemotherapy. As a control group, 68 treated with first-line chemotherapy alone were included. Clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and PD-L1 combined positive score (CPS), were analyzed with regards to the efficacy outcomes.

Results: Progression-free survival (PFS) was longer (median PFS; not reached [NR] vs. 5.2 months, hazard ratio [HR] 0.28, P < 0.001), and overall survival (OS) tended to be longer (median OS; NR vs. 17.9 months, HR 0.43, P = 0.057) in patients treated with nivolumab chemotherapy than those treated with chemotherapy. The PFS benefit of nivolumab chemotherapy over chemotherapy was pronounced in the subgroup with a lower NLR (< 3.80 [median NLR]) (HR 0.10), whereas it was less prominent in patients with a high NLR (≥ 3.80) (HR 0.58). Among patients treated with nivolumab chemotherapy, PFS was worse in patients with a higher NLR (≥ 3.80) than in those with a lower NLR (< 3.80), and survival outcomes were similar between those with PD-L1 CPS ≥ 5 and < 5.

Conclusion: Nivolumab chemotherapy was associated with better efficacy outcomes than chemotherapy alone among patients with d-MMR GC, but survival outcomes were poor even with nivolumab chemotherapy for those with a high NLR. Survival outcomes were not different according to PD-L1 CPS among d-MMR patients treated with nivolumab chemotherapy.

Keywords: Advanced gastric cancer; Deficient mismatch repair protein; Neutrophil-to-lymphocyte ratio; Nivolumab plus chemotherapy; PD-L1 combined positive score.