PO.CL09.03 · 临床研究

伴ARID1A突变的胆道肿瘤（BTT）的临床与基因组学特征：一项病例对照研究

Clinical and genomic characterization of biliary tract tumors (BTT) with ARID1A mutations: A case-control study

编号 5425 展板 15 时间 4/21 09:00–12:00 区域 Section 49 主讲 Angela Lamarca

分会场 Retrospective Observational Studies

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作者与单位 Authors & Affiliations

Giulia Massaro¹, Manuel Pedegral², Diana Rosero¹, Brezo Martinez Amores³, Ester Garcia⁴, Eva Ruiz Hispan¹, Miriam Dorta⁴, Diego Casado⁵, Carlos Garzon⁶, Bernard Gaston Doger de Spéville⁴, Raquel Fuentes¹, Victor Moreno Garcia⁷, Angela Lamarca⁸

¹Fundacion Jimenez Diaz University Hospital, Madrid, Spain,²START-Madrid; Fundacion Jimenez Diaz University Hopsital, Madrid, Spain,³Rey Juan Carlos University Hospital, Madrid, Spain,⁴START-Madrid; Fundacion Jimenez Diaz University Hospital, Madrid, Spain,⁵General de Villalba University Hospital, Madrid, Spain,⁶Infanta Elena University Hospital, Madrid, Spain,⁷START Madrid; Fundacion Jimenez Diaz University Hospital; Health Research Institute-Fundación Jimenez Diaz University Hospital (IIS-FJD), Madrid, Spain,⁸Fundacion Jimenez Diaz University Hospital; Health Research Institute-Fundación Jimenez Diaz University Hospital (IIS-FJD), Madrid, Spain

摘要 Abstract

中文摘要

引言：ARID1A是一种参与染色质重塑的抑癌基因，在多种癌症类型中普遍发生突变。在胆道癌（BTC）中，ARID1A突变的临床与基因组学图谱仍不甚明确。本研究旨在与携带野生型ARID1A（ARID1A-wt）的对照队列相比，刻画ARID1A突变型（ARID1A-mut）BTC患者（pts）的人口学、临床及分子特征。方法：从一个连续入组的146例接受分子谱分析的BTC患者回顾性队列中，14例（9.6%）表现出致病性ARID1A突变。其中13例（8.9%）具有可用临床数据，与随机选取的13例ARID1A-wt对照进行比较。本研究获得当地伦理委员会批准。结果：在筛查的146例患者中，共有27例符合入组条件：14例ARID1A-mut和13例ARID1A-wt。ARID1A-mut患者（对比ARID1A-wt）以女性为主（77% vs 46%；p=0.23）。中位年龄为64岁。原发肿瘤分布为肝内型（76.9%）、肝门型（15.4%）和胆囊型（7.7%）（p=1）。两个队列在诊断时的疾病分期、体能状态及一线（1L）治疗方案方面相当。ARID1A-mut患者对一线治疗表现出更高部分缓解（PR）率的趋势（53.9% vs 30.1%；p=0.43）。一线治疗的中位无进展生存期（PFS）相似（11.4 vs 9.3个月；HR 0.67，95% CI 0.29-1.57；p=0.36），总生存期（OS）亦相似（21.4 vs 22.5个月；HR 1.47，95% CI 0.51-4.28；p=0.48）。基因组谱分析揭示了独特的共改变模式：BAP1（28.6% vs 0%；p=0.09）、IDH1（21.4% vs 0%；p=0.22）和PBRM1（28.6% vs 7.7%；p=0.33）在ARID1A-mut患者中更为常见，而TP53（38.5% vs 28.6%；p=0.69）、KRAS（30.8% vs 16.7%；p=0.38）和DNMT3A（23.1% vs 0%；p=0.09）在ARID1A-WT队列中占主导。结论：伴ARID1A突变的BTC代表了一个独特的分子亚组，其特征为部分缓解改善的趋势以及表观遗传共改变的富集。有必要进行前瞻性验证，以评估其预后和治疗意义。针对BTC中ARID1A的靶向治疗策略应在早期（I/II期）临床试验中进一步探索。

查看英文原文 English abstract

Introduction: ARID1A is a tumor suppressor gene involved in chromatin remodeling and is commonly mutated across several cancer types. In biliary tract cancer (BTC), the clinical and genomic landscape of ARID1A mutations remains poorly defined. This study aims to characterize the demographic, clinical, and molecular features of patients (pts) with ARID1A-mutated (ARID1A-mut) BTC compared with a control cohort harboring wild-type (ARID1A-wt) ARID1A. Methods: From a consecutive retrospective cohort of 146 pts with molecularly profiled BTC, 14 (9.6%) exhibited pathogenic ARID1A mutations. Of these, 13 (8.9%) with available clinical data were compared to a randomly selected group of 13 ARID1A-wt controls. The study was approved by the local ethics committeee. Resuls Out of 146 patients screened, total of 27 were found eligible: 14 ARID1A-mut and 13 ARID1A-wt. ARID1A-mut pts (vs ARID1A-wt) were predominantly female (77% vs 46%; p=0.23). Median age was 64 years. Primary tumor distribution was intrahepatic (76.9%), hilar (15.4%), and gallbladder (7.7%) (p=1). Disease stage at diagnosis, performance status, and first-line (1L) treatment regimens were comparable across both cohorts. ARID1A-mut pts showed a trend toward higher partial response (PR) rates to 1L therapy (53.9% vs 30.1%; p=0.43). Median progression-free survival (PFS) on 1L treatment was similar (11.4 vs 9.3 months; HR 0.67, 95% CI 0.29-1.57; p=0.36), as was overall survival (OS) (21.4 vs 22.5 months; HR 1.47, 95% CI 0.51-4.28; p=0.48). Genomic profiling revealed a distinct co-alteration pattern: BAP1 (28.6% vs 0%; p=0.09), IDH1 (21.4% vs 0%; p=0.22), and PBRM1 (28.6% vs 7.7%; p=0.33) were more frequent in ARID1A-mut pts, whereas TP53 (38.5% vs 28.6%; p=0.69), KRAS (30.8% vs 16.7%; p=0.38), and DNMT3A (23.1% vs 0%; p=0.09) predominated in the ARID1A-WT cohort. Conclusion: BTC with ARID1A mutations represents a distinct molecular subgroup characterized by a trend toward improved partial response and enrichment in epigenetic co-alterations. Prospective validation is warranted to assess the prognostic and therapeutic implications. Targeted therapeutic strategies against ARID1A in BTC should be further explored in early-phase (I/II) clinical trials.

利益披露 Disclosure

G. Massaro, None.. M. Pedegral, None.. D. Rosero, None.. B. Martinez Amores, None.. E. Garcia, None.. E. Ruiz Hispan, None.. M. Dorta, None.. D. Casado, None.. C. Garzon, None.. B. Doger de Spéville, None.. R. Fuentes, None.. V. Moreno Garcia, None. A. Lamarca, see other Other, Travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan, Delcath Advanz Pharma and Roche. Speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA/Novartis, QED, Servier, Astra Zeneca, EISAI, Roche, Advanz Pharma, Jazz Therapeutics and MSD. . see other Other, Advisory and consultancy honoraria from EISAI, Nutricia, Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, AstraZeneca, Boehringer Ingelheim, GENFIT, TransThera Biosciences, Taiho, MSD, JAZZ Therapeutics and Viatris.. see other Principal Investigator-associated Institutional Funding form QED, Merck, Boehringer Ingelheim, Servier, Astra Zeneca, GenFit, Panbela Therapeutics, Novocure GmbH, Camurus AB, Albireo Pharma, Taiho, TransThera, Jazz Therapeutics, Roche, Novartis and Crinetics Pharmaceuticals.

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