Wang Yingnan, Li Yan, Liu Zheng, Liu Jing, Xu Hongmei, Zhang Ruixing, Zhang Fengbin, Guo Zhanjun
Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Oncology, The Handan Central Hospital, Handan, China.
Front Oncol. 2025 Apr 11;15:1476402. doi: 10.3389/fonc.2025.1476402. eCollection 2025.
PD-1 inhibitors combined with chemotherapy have become the standard first-line treatment for advanced gastric cancer (GC), but their efficacy in young GC patients is unknown. This study aimed to evaluate the efficacy of immunotherapy in young GC patients and explore new treatment strategies for this population.
Clinicopathological data of young unresectable GC patients were collected from multiple centres. We defined young as ≤45 years. Statistical analyses were conducted with SPSS IBM for Windows version 24.0.
In total, 225 young unresectable GC patients were registered. Their clinicodemographic characteristics included female predominance (60.9%), poor differentiation (86.7%), high family history of cancer (14.2%), low HER2 expression (12.2%), PD-L1 expression (43.0%) and mismatch repair (MMR) deficiency (1.0%), and a high proportion of peritoneal metastasis (49.3%). After screening, 134 patients were included for analysis: 63 received dual chemotherapy (mFOLFOX6, XELOX, SOX and two-drug containing paclitaxel), 32 PD-1 inhibitors plus dual chemotherapy (mFOLFOX6, XELOX, SOX and two-drug containing paclitaxel), and 39 triple regimens (two-drug chemotherapy combined with apatinib or trastuzumab, or triple chemotherapy based on platinum, fluorouracil and paclitaxel). The effectiveness analysis revealed no significant difference in the disease control rate (DCR) between the dual chemotherapy group and the PD-1 inhibitor plus dual chemotherapy group (=0.787), but triple regimens led to the best DCR (71.4% . 68.8% . 94.9%, all <0.05). Kaplan-Meier curves showed median progression-free survival (PFS) times of the three groups of 4.7, 4.7 and 9.2 months, respectively. The median overall survival (OS) was 13.9, 11.0 and 15.9 months, respectively. Multivariate analyses showed that triple regimens were an independent prognostic factor for PFS [hazard ratio (HR) 0.430, 95% confidence interval (CI) 0.263-0.700; =0.001]. Detailed survival analysis demonstrated that patients receiving intraperitoneal infusion of paclitaxel followed by intravenous paclitaxel combined with S-1 and apatinib oral therapy had better PFS (=0.014) and OS (=0.013) than those receiving other regimens.
Young patients with GC have unique clinical characteristics and are not sensitive to immunotherapy. Triple regimens, especially intraperitoneal infusion of paclitaxel followed by intravenous paclitaxel combined with S-1 and apatinib oral therapy, deserve to be studied as first-line therapies.
程序性死亡受体1（PD-1）抑制剂联合化疗已成为晚期胃癌（GC）的标准一线治疗方案，但其在年轻GC患者中的疗效尚不清楚。本研究旨在评估免疫疗法在年轻GC患者中的疗效，并探索针对该人群的新治疗策略。
从多个中心收集年轻不可切除GC患者的临床病理数据。我们将年轻定义为年龄≤45岁。使用SPSS IBM Windows版本24.0进行统计分析。
共登记了225例年轻不可切除GC患者。他们的临床人口统计学特征包括女性占优势（60.9%）、低分化（86.7%）、癌症家族史高（14.2%）、人表皮生长因子受体2（HER2）低表达（12.2%）、程序性死亡受体配体1（PD-L1）表达（43.0%）和错配修复（MMR）缺陷（1.0%），以及高比例的腹膜转移（49.3%）。筛选后，纳入134例患者进行分析：63例接受双药化疗（改良氟尿嘧啶、亚叶酸钙、奥沙利铂方案[mFOLFOX6]、卡培他滨联合奥沙利铂方案[XELOX]、替吉奥联合奥沙利铂方案[SOX]以及含紫杉醇的两药方案），32例接受PD-1抑制剂联合双药化疗（mFOLFOX6、XELOX、SOX以及含紫杉醇的两药方案），39例接受三联方案（两药化疗联合阿帕替尼或曲妥珠单抗，或基于铂类、氟尿嘧啶和紫杉醇的三联化疗）。疗效分析显示，双药化疗组与PD-1抑制剂联合双药化疗组之间的疾病控制率（DCR）无显著差异（=0.787），但三联方案的DCR最佳（71.4% . 68.8% . 94.9%，均<0.05）。Kaplan-Meier曲线显示，三组的无进展生存期（PFS）中位数分别为4.7、4.7和9.2个月。总生存期（OS）中位数分别为13.9、11.0和15.9个月。多因素分析显示，三联方案是PFS的独立预后因素[风险比（HR）0.430，95%置信区间（CI）0.263 - 0.700；=0.001]。详细的生存分析表明，接受腹腔内注射紫杉醇后静脉注射紫杉醇联合S-1和阿帕替尼口服治疗的患者比接受其他方案的患者具有更好的PFS（=0.014）和OS（=0.013）。
年轻GC患者具有独特的临床特征，对免疫疗法不敏感。三联方案，尤其是腹腔内注射紫杉醇后静脉注射紫杉醇联合S-1和阿帕替尼口服治疗，值得作为一线治疗方案进行研究。
