Gaps in BRCA mutation testing among mCRPC patients: Insights from US cancer practices (2018–2024).

Abstract

102 Background: Treatment of metastatic castration-resistant prostate cancer (mCRPC) has advanced with the approval of poly(ADP-ribose) polymerase inhibitor monotherapy and in combination with androgen receptor pathway inhibitor for patients (pts) with specific homologous recombination repair gene mutations, including BRCA mutations (BRCAm). Access to biomarker targeted therapy requires timely identification of BRCAm through genetic testing. This real-world study aims to characterize BRCAm testing patterns among pts with an mCRPC diagnosis (dx) in US cancer practices. Methods: This retrospective cohort study analyzed electronic health record-derived data from the Flatiron Health Research Database, identifying pts with an mCRPC dx from Jan 1, 2018 to Mar 31, 2024. Pts who participated in a clinical trial were excluded. For eligible pts, records of BRCAm testing during the study period (Jan 1, 2013–Jun 30, 2024) were evaluated. BRCAm testing (yes/no) was assessed by year of mCRPC dx. Multivariable logistic regression was used to estimate differences in the odds of BRCAm testing between pts with different characteristics, selected a-priori (age/year of mCRPC dx, insurance status, care setting, socioeconomic status [SES], race/ethnicity, Gleason score at initial dx, ECOG performance status [ECOG PS] at mCRPC dx, prostate specific antigen [PSA] at mPC dx, and de novo metastatic presentation). Results: This study included 6761 pts with a mCRPC dx in 2018–2024 (median age 75y; 60% White; 80% treated in community settings only; 61% had commercial health insurance). Overall, 3438 (51%) underwent BRCAm testing (1372 [40%] somatic; 804 [23%] germline; 1253 [36%] somatic + germline; 9 [0.3%] unknown). The proportion tested increased by year of mCRPC dx (37% in 2018 to 57% in 2023) but plateaued near 55% in 2020–2024. Regression analyses showed that, among pts who were otherwise similar, the likelihood of BRCAm testing was significantly lower for pts with mCRPC dx at older age (≥65y), whose race/ethnicity was classified as Hispanic/Latino (ethnicity) or other (ie not White, Black/African-American or Asian), with ECOG PS ≥1 or unknown at time of mCRPC dx, had a Gleason score ≤7, or a mCRPC dx before 2020. Differences in the odds of BRCAm testing were too small to estimate with confidence (ie not/borderline significantly different) across insurance status, care setting, SES, PSA at mPC dx, and de novo metastatic presentation. Conclusions: Using data from community oncology centers and academic medical centers in the US, this real-world study found that nearly half of pts diagnosed with mCRPC in 2018–2024 had not undergone BRCAm testing within the review period, which likely limited their access to biomarker-driven therapies. This persistent gap highlights the need to improve BRCAm testing in mCRPC.