Lee Yuna, Kim Hyung-Don, Lee Sun Young, Lee Hyungeun, Hyung Jaewon, Moon Meesun, Shin Jinho, Park Young Soo, Kim Tae Won, Ryu Min-Hee
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Gastric Cancer. 2025 Jul 28. doi: 10.1007/s10120-025-01648-0.
Homologous recombination repair (HRR) gene mutations contribute to genomic instability. However, their clinical value in immune checkpoint inhibitor (ICI)-based treatments in gastric cancer remains unclear. Therefore, this study aims to investigate the efficacy of nivolumab plus chemotherapy according to the HRR mutation status in patients with advanced gastric cancer.
This single-center study included patients with gastric cancer with available panel sequencing results who were treated with first-line nivolumab plus chemotherapy (n = 115) or chemotherapy alone (n = 172). Mutation status of 17 HRR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, RAD52, RAD54L, and XRCC2) was assessed using targeted next-generation sequencing.
Among patients treated with nivolumab plus chemotherapy, 36.5% had HRR mutations, with BRCA2 mutation being the most common mutation (11.3%). Compared to those of the no-HRR mutation group, the HRR mutation group exhibited a higher objective response rate, longer progression-free survival (PFS) (median 12.8 vs. 6.5 months; hazard ratio HR 0.57), and overall survival (OS) (median not reached vs. 14.2 months; HR 0.40) with nivolumab plus chemotherapy. Patients with HRR mutations treated with nivolumab plus chemotherapy showed favorable PFS and OS compared to those treated with chemotherapy alone. However, this difference was not observed in patients without HRR mutations.
HRR mutations were associated with favorable survival outcomes in patients treated with nivolumab plus chemotherapy. Our findings suggest that HRR mutations may serve as a potential predictive biomarker for first-line ICI-based chemotherapy in gastric cancer.
同源重组修复（HRR）基因突变会导致基因组不稳定。然而，它们在胃癌基于免疫检查点抑制剂（ICI）治疗中的临床价值仍不清楚。因此，本研究旨在根据HRR突变状态探讨纳武利尤单抗联合化疗在晚期胃癌患者中的疗效。
本单中心研究纳入了有可用基因检测结果的胃癌患者，这些患者接受一线纳武利尤单抗联合化疗（n = 115）或单纯化疗（n = 172）。使用靶向二代测序评估17个HRR基因（BARD1、BLM、BRCA1、BRCA2、BRIP1、MRE11A、NBN、PALB2、PARP1、POLD1、RAD50、RAD51、RAD51C、RAD51D、RAD52、RAD54L和XRCC2）的突变状态。
在接受纳武利尤单抗联合化疗的患者中，36.5%有HRR突变，其中BRCA2突变是最常见的突变（11.3%）。与无HRR突变组相比，HRR突变组在接受纳武利尤单抗联合化疗时表现出更高的客观缓解率、更长的无进展生存期（PFS）（中位值12.8个月对6.5个月；风险比HR 0.57）和总生存期（OS）（中位值未达到对14.2个月；HR 0.40）。与单纯接受化疗的患者相比，接受纳武利尤单抗联合化疗的HRR突变患者表现出良好的PFS和OS。然而，在无HRR突变的患者中未观察到这种差异。
HRR突变与接受纳武利尤单抗联合化疗患者的良好生存结果相关。我们的研究结果表明，HRR突变可能作为胃癌一线基于ICI化疗的潜在预测生物标志物。
