Chen Tianran, Xu Meng, Xu Jiajun, Zhan Xianbao, Zhang Yingyi, Ying Mingzhen, Wu Meihong
Department of Oncology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, P.R. China.
Mol Clin Oncol. 2024 Nov 21;22(1):11. doi: 10.3892/mco.2024.2806. eCollection 2025 Jan.
Human epidermal growth factor receptor-2 (HER2) negative advanced gastric cancer (GC) has a high global incidence and mortality rate with limited options for second-line treatment. Monotherapy is not effective and the combination of chemotherapy and immunotherapy has not yet been included in the guidelines. The present study aimed to explore a new treatment approach by conducting a single-center, retrospective, observational real-world study. A total of 21 patients with advanced HER2-negative GC, who had progressed after receiving standard first-line regimens [tegafur, gimeracil and oteracil potassium capsules (S-1) or capecitabine plus oxaliplatin], were selected. The application of programmed cell death-1 (PD-1) inhibitor combined with taxanes was selected as the second-line treatment. The primary outcomes measured were progression-free survival (PFS), pathological complete response, objective response rate (ORR), disease control rate (DCR) and adverse reactions in the present patient cohort. The median (m)PFS in the overall population was 7.1 months, with a 95% confidence interval (CI) of 6.0-8.2 months and the median overall survival (mOS) was 11.3 months, with a 95% CI of 4.5-18.2 months. The ORR was 9.5% and the DCR was 90.5%. Univariate and multivariate analyses indicated that Ki67 <70% and tumor marker-positive status [one or two increases among carcinoembryogenic antigen (CEA), cancer antigen (CA) 199 and CA125] were independent prognostic factors for PFS and overall survival (OS) in second-line treatment. Significant statistical differences were noted in PFS (mPFS=5.3 months, 95% CI: 3.1-7.5 months vs. mPFS=9.1 months, 95% CI: 6.2-12.0 months; P=0.002) and OS (mOS=8.8 months, 95% CI: 7.0-10.7 months vs. mOS=17.2 months, 95% CI: 16.0-18.5 months; P=0.013) between the Ki67-high group (Ki67 ≥70%) and the Ki67-low group (Ki67 <70%). Significant statistical differences were noted in OS between tumor marker-negative status (CEA, CA199 and CA125 within normal range) and tumor marker-positive status (one or two increases among CEA, CA199 and CA125; mOS=17.2 months, 95% CI: 16.0-18.4 months vs. mOS=8.8 months, 95% CI: 5.3-12.4 months; P=0.018); however, no significant differences were noted in PFS between these two groups. The present study retrospectively analyzed the new second-line approach of PD-1 inhibitor combined with taxanes for HER2 negative GC which effectively improved patient PFS and OS compared with single-agent chemotherapy. The expression levels of Ki67 and the tumor marker-negative status possess potential clinical value in monitoring prognosis and guiding future individualized use of chemotherapy combined with immunotherapy.
人表皮生长因子受体2（HER2）阴性晚期胃癌（GC）在全球范围内发病率和死亡率较高，二线治疗选择有限。单药治疗无效，化疗与免疫治疗的联合方案尚未纳入指南。本研究旨在通过开展一项单中心、回顾性、观察性真实世界研究来探索一种新的治疗方法。共纳入21例HER2阴性晚期胃癌患者，这些患者在接受标准一线治疗方案[替吉奥胶囊（S-1）或卡培他滨联合奥沙利铂]后病情进展。选择程序性细胞死亡蛋白1（PD-1）抑制剂联合紫杉烷类药物作为二线治疗方案。主要观察指标为无进展生存期（PFS）、病理完全缓解、客观缓解率（ORR）、疾病控制率（DCR）及本患者队列中的不良反应。总体人群的中位PFS为7.1个月，95%置信区间（CI）为6.0 - 8.2个月，中位总生存期（mOS）为11.3个月，95%CI为4.5 - 18.2个月。ORR为9.5%，DCR为90.5%。单因素和多因素分析表明，Ki67<70%以及肿瘤标志物阳性状态[癌胚抗原（CEA）、癌抗原（CA）199和CA125中一项或两项升高]是二线治疗中PFS和总生存期（OS）的独立预后因素。Ki67高表达组（Ki67≥70%）和Ki67低表达组（Ki67<70%）之间在PFS（mPFS = 5.3个月，95%CI：3.1 - 7.5个月 vs. mPFS = 9.1个月，95%CI：6.2 - 12.0个月；P = 0.002）和OS（mOS = 8.8个月，95%CI：7.0 - 10.7个月 vs. mOS = 17.2个月，95%CI：16.0 - 18.5个月；P = 0.013）方面存在显著统计学差异。肿瘤标志物阴性状态（CEA、CA199和CA125在正常范围内）与肿瘤标志物阳性状态（CEA、CA199和CA125中一项或两项升高；mOS = 17.2个月，95%CI：16.0 - 18.4个月 vs. mOS = 8.8个月，95%CI：5.3 - 12.4个月；P = 0.018）之间在OS方面存在显著统计学差异；然而，两组之间在PFS方面未观察到显著差异。本研究回顾性分析了PD-1抑制剂联合紫杉烷类药物用于HER2阴性GC的新二线治疗方法，与单药化疗相比，该方法有效改善了患者的PFS和OS。Ki67表达水平和肿瘤标志物阴性状态在监测预后及指导未来化疗联合免疫治疗的个体化应用方面具有潜在临床价值。
