Real-world homologous recombination repair (HRR) mutation testing patterns in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in the United States (US).

Abstract

99 Background: A subset of pts with metastatic prostate cancer have HRR mutations. These can be either germline or somatic mutations. Previous studies have established a prognostic and predictive role of HRR mutations and there are ongoing trials (e.g., TALAPRO-3, AMPLITUDE) exploring combination strategies of poly-ADP ribose polymerase inhibitors (PARPi) with novel hormonal therapies (NHT). Therefore, it is relevant to establish baseline HRR testing rates in the real-world setting. This study assessed real-world (rw) HRR testing patterns in pts with mCSPC in the US and described characteristics of tested vs untested pts. Methods: Data were drawn from the Adelphi Prostate Cancer Disease Specific Programme; a point-in-time questionnaire administered to oncologists and urologists in the US between January-August 2020. Physicians abstracted medical records for the next 4-9 pts receiving active drug treatment for mCSPC. Study variables included pt demographics, clinical factors, physician characteristics, and testing status for at least 1 of 12 HRR genes of interest ( ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C). Pt demographics and clinical characteristics were compared between groups using t-tests for continuous and chi-squared or Fisher’s exact test for categorical variables. A multiple logistic regression model was used to assess factors associated with odds of HRR testing. Results: A total of 71 physicians reported on 204 pts with mCSPC. The median age was 68.8. 57/204 (28%) pts were tested for HRR mutations using germline or tumor testing. Pts who were not HRR tested were older compared to HRR tested pts (69.6 vs 66.8, P = 0.038). More pts currently receiving care by an oncologist had a HRR mutation test vs. pts currently receiving care by a urologist [50/156 (32%) vs 7/48 (15%), P =0.02]. According to the multiple logistic regression model, having a known family history of prostate cancer [OR = 3.9 (95% CI: 1.1 – 13.6); P = 0.04], and having visceral metastases at mCSPC diagnosis [OR=4.9 (95% CI: 2.0 – 12.1); P = 0.001] were associated with a significantly higher odds of receiving a HRR mutation test. Conclusions: In this rw US study of adult patients with mCSPC, most patients did not receive HRR testing. Disparities in HRR mutation testing were observed, suggesting that clinical characteristics may influence decisions to test for HRR mutations. Focused efforts to increase HRR mutation testing should be implemented.