PO.CL09.01 · 临床研究

在一个基于美国的真实世界临床基因组数据库中，按年龄、种族/族裔和组织学类型分析卵巢癌叶酸受体α表达的流行病学

Epidemiology of folate receptor alpha expression in ovarian cancer by age, race/ethnicity, and histotype in a real-world, US-based clinicogenomic database

编号 5351 展板 19 时间 4/21 09:00–12:00 区域 Section 46 主讲 Rebecca Arend, MD

分会场 Precision Oncology and Real World Data

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作者与单位 Authors & Affiliations

Rebecca C. Arend¹, Kent F. Hoskins², Jenny S. Guadamuz³, Gregory S. Calip⁴, Megan A. Clarke⁴, Yookyung Christy Choi⁴, Qu Zhang⁴, Ricardo R. Lastra⁵, Amanda L. Strickland⁶, Sarah K. Lynam⁷

¹University of Alabama at Birmingham, Birmingham, AL,²University of Illinois Chicago, Chicago, IL,³University of California Berkeley, Berkeley, CA,⁴AbbVie, Inc., North Chicago, IL,⁵The University of Chicago, Chicago, IL,⁶University of North Carolina at Chapel Hill, Chapel Hill, NC,⁷University Hospitals Seidman Cancer Center, Cleveland, OH

摘要 Abstract

中文摘要

卵巢癌（OC）在分子层面具有异质性，需要生物标志物来指导个体化治疗。叶酸受体α（FRα）是一个具有治疗意义的可干预生物标志物。我们利用真实世界美国临床基因组数据，按年龄、种族/族裔和组织学类型评估OC中FRα的表达。我们利用与Caris Life Sciences基因组数据链接的ConcertAI RWD360™数据库，对2019年至2025年诊断为卵巢癌、输卵管癌或原发性腹膜癌的患者进行了横断面分析。FRα检测使用VENTANA FOLR1（FOLR1-2.1）RxDx检测（Roche Diagnostics）进行；FRα高定义为≥75%的肿瘤细胞具有≥2+膜染色。使用改良的Poisson回归估计分层患病率和多变量患病率比（RR）及其95% CI。敏感性分析和探索性分析评估了在完整、未经筛选的OC临床基因组数据库中与FRα表达的关联，应用一个基于全转录组RNAseq训练的、经过验证的机器学习分类器来预测FRα高表达（N=3045）。在1155例接受FRα检测的OC患者中，中位年龄为66岁（y）（IQR，58-73）；71%为非西班牙裔白人，61%为高级别浆液性组织学。33%观察到FRα高表达，其中高级别浆液性（43%）的患病率高于较少见的组织学类型（低级别浆液性，24%；子宫内膜样，6%；透明细胞，2%；癌肉瘤，9%）（P<0.001）。在校正组织学类型后，FRα高患病率与年龄之间无显著关联（<50，参照；50-64，aRR 0.95，95% CI 0.69-1.31；65-74，aRR 1.15，95% CI 0.84-1.57；≥75岁，aRR 1.18，95% CI 0.85-1.63）。FRα高患病率在各种族/族裔间无差异（P=0.933），包括在校正年龄和组织学类型后：非西班牙裔黑人，34%（aRR 1.03 [95% CI，0.78-1.35]）；非西班牙裔亚裔，29%（aRR 0.97，95% CI 0.57-1.65）；西班牙裔，30%（aRR 0.95，95% CI 0.64-1.40）；非西班牙裔白人（32%，参照）。在限于高级别浆液性组织学的敏感性分析中，观察到与年龄和种族/族裔一致的关联。在探索性分析中，在更广泛的数据库中观察到相似的关联。 FRα高表达在年龄或种族/族裔群体间无显著差异，且在高级别浆液性OC中最为普遍。这些发现进一步支持FRα作为一个在各人口统计学群体中具有广泛临床适用性的OC生物标志物，并证明了在FRα高患病率研究中考虑组织学类型潜在混杂因素的重要性。在晚期OC的诊疗评估中进一步采用FRα检测可提供重要信息，以确保患者能够获得所有符合条件的治疗选择和生物标志物导向的临床试验，尤其是对于代表性不足的群体和面临医疗资源可及性差异的群体。

查看英文原文 English abstract

Ovarian cancer (OC) is molecularly heterogeneous, requiring biomarkers to guide personalized therapy. Folate receptor alpha (FR⍺) is an actionable biomarker with therapeutic implications. We evaluated FR⍺ expression in OC by age, race/ethnicity, and histotype using real-world US clinicogenomic data. We conducted a cross-sectional analysis of patients diagnosed with ovarian, fallopian tube, or primary peritoneal cancer from 2019 to 2025 using the ConcertAI RWD360™ database linked to Caris Life Sciences genomic data. FR⍺ testing was done using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay (Roche Diagnostics); FR⍺-high was defined as ≥75% of tumor cells with ≥2+ membrane staining. Stratified prevalence rates and multivariable prevalence rate ratios (RRs) with 95% CIs were estimated using modified Poisson regression. Sensitivity and exploratory analyses evaluated associations with FR⍺ expression in the full, unselected OC clinicogenomic database, applying a validated machine learning classifier trained on whole transcriptome RNAseq to predict FR⍺-high expression (N=3045). Among 1155 patients with OC who received FR⍺ testing, median age was 66 years (y) (IQR, 58-73); 71% were non-Hispanic White and 61% had high-grade serous histology. FR⍺-high expression was observed in 33%, with higher prevalence in high-grade serous (43%) compared to less common histotypes (low-grade serous, 24%; endometrioid, 6%; clear cell, 2%; carcinosarcoma, 9%) ( P <0.001). There were no significant associations between FR⍺-high prevalence and age after adjusting for histotype (<50, Reference; 50-64, aRR 0.95, 95% CI 0.69-1.31; 65-74, aRR 1.15, 95% CI 0.84-1.57; ≥75 y, aRR 1.18, 95% CI 0.85-1.63). FR⍺-high prevalence did not differ by race/ethnicity ( P =0.933) including after adjustment for age and histotype: non-Hispanic Black, 34% (aRR 1.03 [95% CI, 0.78-1.35]); non-Hispanic Asian, 29% (aRR 0.97, 95% CI 0.57-1.65); Hispanic, 30% (aRR 0.95, 95% CI 0.64-1.40); non-Hispanic White (32%, Reference). In sensitivity analyses restricted to high-grade serous histology, consistent associations with age and race/ethnicity were observed. In exploratory analyses, similar associations were observed in the broader database. FR⍺-high expression does not significantly differ by age or racial/ethnic group and is most prevalent in high-grade serous OC. These findings further support FR⍺ as an OC biomarker with broad clinical applicability across demographics and demonstrate the importance of accounting for potential confounding by histotype in studies of FR⍺-high prevalence. Further adoption of FR⍺ testing in the work-up for advanced OC provides important information to ensure patients have access to all eligible treatment options and biomarker-directed clinical trials, particularly for underrepresented groups and those facing disparities in access to healthcare.

利益披露 Disclosure

R. C. Arend, AbbVie, Inc. ). AstraZeneca ). GSK ). Champions Oncology ). Tempus ). LifeNet ). Artera ). K. F. Hoskins, Merck Sharp & Dohme ). Novartis Pharmaceuticals UK Ltd. ). AbbVie, Inc. ). Pfizer, Inc. ). Genentech, Inc. ). Agendia, Inc. ). J. S. Guadamuz, Robert Wood Johnson Foundation ), Travel. Flatiron Health Other, consulting fees. Society for Epidemiologic Research Travel, Other, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events. G. S. Calip, AbbVie, Inc. Employment, Stock. M. A. Clarke, AbbVie, Inc. Employment, Stock. Y. Choi, AbbVie, Inc. Employment, Stock. Q. Zhang, AbbVie, Inc. Employment, Stock. R. R. Lastra, AbbVie, Inc. Other, Advisory Board. ArsenalBio Other, Independent Consultant. GlaxoSmithKlein Other, Advisory Board. A. L. Strickland, None. S. K. Lynam, AbbVie, Inc. Other, Advisory Board.

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