Combined Chemotherapy-Immunotherapy for Advanced Biliary Tract Cancer (BTC): A Clinical, Genomic, and Biomarker Analysis.

IF 1.6 Q4 ONCOLOGY

Journal of Gastrointestinal Cancer Pub Date : 2025-04-01 DOI:10.1007/s12029-025-01215-x

Yong Zhang, Miaomiao Gou

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引用次数: 0

Abstract

Background: Biliary tract cancer (BTC) represents a heterogeneous disease spectrum associated with an unfavorable prognosis. A combination of immunotherapy and chemotherapy has become a new standard strategy for advanced BTC. However, understanding the association between genomic alterations and outcomes of immunotherapy in BTC is crucial for further improving clinical benefits.

Method: Patients with metastatic BTC were included in this study retrospectively, who received PD-1/PD-L1 (ICI) antibodies combined with chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall response rate (ORR) and disease control rate (DCR). Additionally, we conducted exploratory analysis of genomic alterations and biomarkers.

Results: Ninety-one patients were enrolled in this study. The patients were divided into two groups: albumin paclitaxel + S1 (AS) + PD-1 (n = 56) group and GC + ICI (n = 35) group. There were no significant differences in terms of PFS, ORR, and DCR between the two groups. Regarding biomarker analysis, 44 patients had positive PD-L1 expression, with a mPFS of 4.8 months and an ORR of 15.9%. Surprisingly, 29 patients had negative PD-L1 expression, with a mPFS of 9.9 months and an ORR of 27.6%. The average tumor mutational burden (TMB) was 4.5 mutations per megabase (mut/MB) for patients with microsatellite-stable (MSS) tumors. There was no significant difference in PFS between patients with TMB high and low (cutoff = 4.5 mut/MB). Genomic analysis revealed TP53 (n = 13, 43.3%), KRAS (n = 8, 26.7%), NTRK1/2/3 (n = 8, 26.7%), isocitrate dehydrogenase (IDH) 1/2 (n = 6, 20.0%), PIK3CA (n = 6, 20.0%), BRCA2 (n = 5, 16.7%), MDM2/4 (n = 5, 16.7%), and BRAF (n = 4, 13.3%) as the most common gene alterations. MDM2/4 mutations were associated with shorter survival (p < 0.05).

Conclusion: GC plus immunotherapy is still the standard of care for late stage BTC. PD-L1 expression and TMB were not good predictors for selecting patients who would benefit more from immunotherapy plus chemotherapy.

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化疗-免疫联合治疗晚期胆道癌（BTC）：临床、基因组和生物标志物分析。

背景：胆道癌（BTC）是一种与不良预后相关的异质性疾病。免疫联合化疗已成为晚期BTC治疗的新标准策略。然而，了解基因组改变与BTC免疫治疗结果之间的关系对于进一步提高临床疗效至关重要。方法：回顾性研究转移性BTC患者，接受PD-1/PD-L1 （ICI）抗体联合化疗。主要终点是无进展生存期（PFS），次要终点包括总缓解率（ORR）和疾病控制率（DCR）。此外，我们对基因组改变和生物标志物进行了探索性分析。结果：91例患者入组。将患者分为白蛋白紫杉醇+ S1 (AS) + PD-1组（n = 56）和GC + ICI组（n = 35）。两组患者的PFS、ORR和DCR均无显著差异。在生物标志物分析方面，44例患者PD-L1表达阳性，mPFS为4.8个月，ORR为15.9%。令人惊讶的是，29例患者PD-L1表达为阴性，mPFS为9.9个月，ORR为27.6%。微卫星稳定型（MSS）肿瘤患者的平均肿瘤突变负担（TMB）为每兆碱基4.5个突变（mut/MB）。TMB高、低患者的PFS无显著差异（截止值= 4.5 mut/MB）。基因组分析显示，TP53 （n = 13, 43.3%）、KRAS （n = 8, 26.7%）、NTRK1/2/3 （n = 8, 26.7%）、异柠檬酸脱氢酶（IDH） 1/2 （n = 6, 20.0%）、PIK3CA （n = 6, 20.0%）、BRCA2 （n = 5, 16.7%）、MDM2/4 （n = 5, 16.7%）和BRAF （n = 4, 13.3%）是最常见的基因改变。MDM2/4突变与较短的生存期相关(p)结论：GC +免疫治疗仍然是晚期BTC的标准治疗方案。PD-L1表达和TMB并不能很好地预测选择从免疫治疗和化疗中获益更多的患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gastrointestinal Cancer ONCOLOGY-

CiteScore

3.80

自引率

0.00%

发文量

121

期刊介绍： The Journal of Gastrointestinal Cancer is a multidisciplinary medium for the publication of novel research pertaining to cancers arising from the gastrointestinal tract.The journal is dedicated to the most rapid publication possible.The journal publishes papers in all relevant fields, emphasizing those studies that are helpful in understanding and treating cancers affecting the esophagus, stomach, liver, gallbladder and biliary tree, pancreas, small bowel, large bowel, rectum, and anus. In addition, the Journal of Gastrointestinal Cancer publishes basic and translational scientific information from studies providing insight into the etiology and progression of cancers affecting these organs. New insights are provided from diverse areas of research such as studies exploring pre-neoplastic states, risk factors, epidemiology, genetics, preclinical therapeutics, surgery, radiation therapy, novel medical therapeutics, clinical trials, and outcome studies.In addition to reports of original clinical and experimental studies, the journal also publishes: case reports, state-of-the-art reviews on topics of immediate interest or importance; invited articles analyzing particular areas of pancreatic research and knowledge; perspectives in which critical evaluation and conflicting opinions about current topics may be expressed; meeting highlights that summarize important points presented at recent meetings; abstracts of symposia and conferences; book reviews; hypotheses; Letters to the Editors; and other items of special interest, including:Complex Cases in GI Oncology: This is a new initiative to provide a forum to review and discuss the history and management of complex and involved gastrointestinal oncology cases. The format will be similar to a teaching case conference where a case vignette is presented and is followed by a series of questions and discussion points. A brief reference list supporting the points made in discussion would be expected.