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转移性胃癌一线化疗免疫治疗进展后继续使用PD-1抑制剂的临床获益及生物标志物探索

Clinical benefit of continuation of PD-1 inhibitors after progression on first-line chemoimmunotherapy in metastatic gastric cancer and biomarker exploration.

作者信息

Zhang Mengwei, Bai Long, Chen Jianwen, Meng Qi, Lu Yunxin, Zhang Dongsheng

机构信息

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University, Guangzhou, 510060, P. R. China.

Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, P. R. China.

出版信息

BMC Cancer. 2025 May 24;25(1):935. doi: 10.1186/s12885-025-14286-7.

DOI:10.1186/s12885-025-14286-7
PMID:40413463
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12103759/
Abstract

BACKGROUND

Whether continuing immunotherapy after progression in second-line settings of metastatic gastric cancer (MGC) remains unclear. Herein, we explored the efficacy of PD-1 inhibitors for MGC after progression on previous chemoimmunotherapy.

METHODS

We retrospectively identified MGC patients who received oxaliplatin-based chemotherapy plus PD-1 inhibitor, with or without trastuzumab, as first-line treatment. The patients received treatment with or without PD-1 inhibitors beyond progression in patients with MGC were divided into treatment beyond progression (TBP) group and non-TBP (NTBP) group. The median progression free survival (PFS) and overall survival (OS) from the start of treatment after progression were assessed.

RESULTS

The mOS and mPFS in the TBP group was significantly longer than that in the NTBP group (mOS: 9.0 vs. 5.0 months, P = 0.011; mPFS: 4.3 vs. 2.7 months, P = 0.03). Moreover, TBP was an independent prognostic factor for both PFS and OS in multivariate analysis. In the subgroup analysis, patients who were male, had a favorable ECOG (0-1), classified into diffuse histologic subtype and achieved disease control in the prior chemoimmunotherapy, might be more likely to benefit from continuing immunotherapy compared to discontinuation beyond progression.

CONCLUSION

PD-1 inhibitors based therapeutic strategy may be a reasonable option in second-line setting for MGC who progressed on prior immunotherapy. Further larger prospective trials are warranted to validate these findings.

摘要

背景

在转移性胃癌(MGC)二线治疗中,疾病进展后继续进行免疫治疗的效果仍不明确。在此,我们探讨了PD-1抑制剂用于既往接受过化疗联合免疫治疗后疾病进展的MGC患者的疗效。

方法

我们回顾性纳入了接受以奥沙利铂为基础的化疗联合PD-1抑制剂(有或无曲妥珠单抗)作为一线治疗的MGC患者。将疾病进展后接受或未接受PD-1抑制剂治疗的MGC患者分为疾病进展后治疗(TBP)组和非TBP(NTBP)组。评估自疾病进展后开始治疗的中位无进展生存期(PFS)和总生存期(OS)。

结果

TBP组的中位总生存期(mOS)和中位无进展生存期(mPFS)显著长于NTBP组(mOS:9.0个月对5.0个月,P = 0.011;mPFS:4.3个月对2.7个月,P = 0.03)。此外,在多因素分析中,TBP是PFS和OS的独立预后因素。在亚组分析中,与疾病进展后停药相比,男性、东部肿瘤协作组(ECOG)状态良好(0-1)、组织学类型为弥漫型且在既往化疗联合免疫治疗中实现疾病控制的患者可能更有可能从继续免疫治疗中获益。

结论

对于既往免疫治疗后疾病进展的MGC患者,基于PD-1抑制剂的治疗策略可能是二线治疗中的合理选择。需要进一步开展更大规模的前瞻性试验来验证这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/815d88d862b5/12885_2025_14286_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/ddb11788054f/12885_2025_14286_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/e4755a558a0a/12885_2025_14286_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/2db1f603305b/12885_2025_14286_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/6a6847aa4129/12885_2025_14286_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/be7f58a42dcc/12885_2025_14286_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/815d88d862b5/12885_2025_14286_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/ddb11788054f/12885_2025_14286_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/e4755a558a0a/12885_2025_14286_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/2db1f603305b/12885_2025_14286_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/6a6847aa4129/12885_2025_14286_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/be7f58a42dcc/12885_2025_14286_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/12103759/815d88d862b5/12885_2025_14286_Fig6_HTML.jpg

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