Patterns of poly(ADP-ribose) polymerase inhibitor use and overall survival in United States veterans with prostate cancer.

Abstract

e17049 Background: PARP inhibitors (PARPi) are life-prolonging therapies for men with homologous recombination repair (HRR) deficient metastatic castration-resistant prostate cancer (mCRPC). While studies have reported improved clinical outcomes from PARPi, estimates of benefit in diverse patient populations are limited. Here we describe patterns of PARPi use and outcomes in mCRPC in the Veterans Health Administration (VA), which includes a high proportion of Black patients, otherwise significantly underrepresented in the published PARPi studies. Methods: This retrospective cohort included mCRPC patients prescribed a PARPi in the US national VA Healthcare System. Data collection included demographic, clinical, pathologic, and genomic data. Descriptive statistics and survival analyses were conducted, using inverse probability of treatment weighting (IPTW) to adjust for baseline differences by race (Gleason score, prior prostatectomy, stage IV at diagnosis, number of systemic therapies, age at diagnosis, PSA at diagnosis, and PSA at start of PARPi). The primary outcome was overall survival (OS), defined as time from PARPi initiation to death from any cause or censoring. Other outcomes included percent PSA change from baseline, time on PARPi, and genomics-stratified OS. Results: Among 597 Veterans, 79.4% were White and 20.6% Black. Compared to White men, Black men were younger (62 versus 68 yrs), had higher median PSA at diagnosis (19.0 versus 8.8 ng/mL), longer time from diagnosis to PARPi initiation (90.6 versus 69.4 mos), and were more commonly treated with PARPi as ≥4 th line therapy (43.9 versus 31.4%). Median OS from PARPi initiation was 13.7 months (95% CI 12.6-15.8), with no statistically significant difference between Black and White patients after IPTW (p = 0.95). In PSA responders, median time to best PSA response was 5.1 months (IQR 2.7-8.4). The most common HRR variants were BRCA2 , ATM , or CDK12 . In exploratory analyses, patients with BRCA alterations had longer OS than those without (median 15.9 vs 12.6 mos). Black patients with CDK12 alterations had longer OS than those without (median 21.4 vs 12.2 mos). Conclusions: In this real-world cohort of Veterans with mCRPC, Black patients were noted to have higher risk disease and received PARPi later in the course of their prostate cancer, pointing to the need to address equity in practice patterns. After adjustment for baseline differences, survival on PARPi was similar by race. Further research on CDK12 mutations and PARPi response, especially in Black patients, is warranted.