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

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.