(UroToday.com) The 2025 ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Hiba Khan discussing the uptake of targeted therapy in a large cohort of patients with advanced prostate cancer and germline pathogenic variants.
Men with advanced prostate cancer and pathogenic germline variants in homologous recombination repair (HRR) or mismatch repair (MMR) genes are eligible for targeted therapies, namely PARP inhibitors, platinum chemotherapy, or immune checkpoint inhibitors. The influence of these pathogenic germline variants on uptake of targeted therapies is understudied and necessary to identify and intervene upon possible disparities. At the 2025 ASCO annual meeting, Dr. Khan described prostate cancer targeted treatment patterns in men with advanced prostate cancer.
Germline genetic testing and insurance claims data (Komodo Healthcare MapTM) were assembled for advanced prostate cancer (defined by ICD10/CPT codes) patients diagnosed from 2015-2024 with ≥ 1 year of claims pre-diagnosis. Treatment uptake by germline genetic testing results were compared with Χ2 tests (negative/variant of uncertain significance versus HRR/MMR pathogenic germline variants) and multivariable logistic regression (negative/variant of uncertain significance versus BRCA1/BRCA2, other HRR/MMR pathogenic germline variants).
Overall, 11,545 men with advanced prostate cancer underwent germline genetic testing: 66% White, 50% commercial insurance, 27% prostate cancer family history, with a mean age at diagnosis of 65 years. There were 924 (8%) and 145 (1%) men that had ≥1 pathogenic germline variants in an HRR or MMR gene, respectively. With regards to treatment, 1,246 (11%) men received platinum chemotherapy, 332 (3%) received PARP inhibitors, and 521 (5%) received immune checkpoint inhibitors.
Men with HRR pathogenic germline variants were more likely than men with variant of uncertain significance/negative results to receive platinum chemotherapy (14% versus 11%, p = 0.001) and PARP inhibitors (16% HRR, 25% BRCA1/2 versus 2%, p < 0.001 for both), and men with MMR pathogenic germline variants were more likely to receive immune checkpoint inhibitors (19% versus 4%, p < 0.001). Black men had lower odds of platinum chemotherapy and immune checkpoint inhibitors than White men, but higher odds of PARP inhibitors. Among men with HRR pathogenic germline variants, Black men and those with BRCA1/2 pathogenic germline variants were more likely to receive PARP inhibitors:
Dr. Khan concluded her presentation discussing the uptake of targeted therapy in a large cohort of patients with advanced prostate cancer and germline pathogenic variants with the following take home points:
- Less than 1 in 4 men with advanced prostate cancer and HRR/MMR pathogenic germline variants received appropriate targeted therapies
- PARP inhibitor uptake among eligible patients was twice as high among Black men compared to White men, perhaps reflecting clinician perception of more aggressive disease; rates of platinum chemotherapy and immune checkpoint inhibitors were not similarly higher
- These findings raise questions about appropriate receipt of targeted agents and future studies should qualitatively assess clinician prescribing patterns, including sequencing of therapies as approvals for first line PARP inhibitors expand
Presented by: Hiba M. Khan, MD, MPH, University of Washington, Fred Hutch Cancer Center, Seattle, WA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.