Uptake of targeted therapy in a large cohort of patients with advanced prostate cancer and germline pathogenic variants.

Abstract

5049 Background: Men with advanced prostate cancer (PrCa) and pathogenic germline variants (PGV) in homologous recombination repair (HRR) or mismatch repair (MMR) genes are eligible for targeted therapies, namely poly (ADP-ribose) polymerase inhibitors (PARPi), platinum chemotherapy, or immune checkpoint inhibitors (ICI). The influence of these PGV on uptake of targeted therapies is understudied and necessary to identify and intervene upon possible disparities. We describe PrCa targeted treatment patterns in men with advanced PrCa. Methods: Germline genetic testing (GGT) (Labcorp) and insurance claims data (Komodo Healthcare MapTM) were assembled for advanced PrCa (defined by ICD10/CPT codes) patients diagnosed from 2015-2024 with ≥ 1 year of claims pre-diagnosis. Treatment uptake by GGT result were compared with Χ 2 tests (negative/variant of uncertain significance (VUS), vs HRR/MMR PGV) and multivariable logistic regression (negative/VUS vs BRCA1/BRCA2 , other HRR/MMR PGV) (Table). Results: 11,545 men with advanced PrCa underwent GGT: 66% White, 50% commercial insurance, 27% PrCa family history, mean age at diagnosis: 65. 924 (8%) and 145 (1%) of men had ≥1 PGV in a HRR or MMR gene, respectively. 1,246 (11%) men received platinum chemotherapy, 332 (3%) received PARPi and 521 (5%) received ICI. Men with HRR PGV were more likely than men with VUS/negative results to receive platinum chemo (14% vs. 11%, p=0.001) and PARPi (16% HRR, 25% BRCA1/2 vs. 2%, p<0.001 for both) and men with MMR PGV were more likely to receive ICI (19% vs. 4%, p<0.001). Black men had lower odds of platinum chemo and ICI than White men, but higher odds of PARPi . Among men with HRR PGV, Black men and those with BRCA1/2 PGV were more likely to receive PARPi (Table). Conclusions: Less than 1 in 4 men with advanced PrCa and HRR/MMR PGV received appropriate targeted therapies. PARPi 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 chemo and ICI 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 PARPi expand. Multivariable analysis of factors associated (p<0.05) with targeted therapy uptake. Platinum chemoOR (CI) ICIOR (CI) PARPiOR (CI) PARPi (HRR PGV only)OR (CI) History of non-prostate cancer 12 (10-14) 12 (9-16) 1.4 (1-2) NS Positive GGT result (ref: negative/VUS) (ref: other HRR) BRCA1/BRCA2 NS NA 18 (14-24) 4 (3-6) Other HRR NS NA 5 (3-7) NA MMR NA 3 (2-5) NA NA Black race/ethnicity (ref: White) 0.7 (0.6-0.9) 0.4 (0.3-0.7) 1.9 (1-3) 2 (1-4) OR, odds ratio; CI, 95% confidence interval; NA, not applicable; NS, not significant. NS factors not shown: insurance, age at diagnosis, age2, family history of PrCa, geographic region.