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e17028 Background: Men of African ancestry have a disproportionately higher incidence of prostate cancer than Caucasians. Yet, men of African ancestry have historically been underrepresented in clinical trials for metastatic prostate cancer (MPC). Further, differences in the magnitude of clinical benefit from treatment by race have been reported. The objective of this study was to assess the racial disparities in clinical trial enrollment of men with MPC and the magnitude of difference in clinical benefit between men of African ancestry and Caucasians with MPC. Methods: A systematic review of MEDLINE was conducted to identify studies published between January 2001 to May 2021. We included: (a) studies that enrolled adults with metastatic castration-resistant prostate cancer (mCRPC) or metastatic hormone sensitive prostate cancer; (b) clinical trials with complete race-stratified frequencies for enrolled subjects; or (c) clinical trials or observational studies that reported race-stratified subgroup analyses or adjusted effect estimates for efficacy/effectiveness outcomes. Outcome measures included overall survival (OS) and progression-free survival (PFS). Results: Of 2,140 retrieved articles, 39 studies involving 39,181 subjects met eligibility criteria. The majority of the studies (n = 35) enrolled mCRPC subjects. Of the 39 studies, 24 were clinical trials and 15 were observational studies. Twenty-one studies enrolled only patients in the US while 18 were multinational studies. Of the 15,761 subjects enrolled in clinical trials, 1750 (11.1%) were men of African ancestry and 12,321 (78.1%) Caucasian. The median (interquartile range) enrollment rate of men of African ancestry in clinical trials was 5.7% (2.3%, 10.1%). Of the 39 eligible studies, 15 reported race-stratified clinical outcomes. Three studies compared men of African ancestry vs Caucasians, 2 men of African ancestry vs non-African ancestry, 3 Caucasian vs others or vice-versa. The remaining 7 studies reported separate estimates on survival by race. All 5 studies comparing men of African ancestry versus other racial groups were conducted in mCRPC subjects. No difference in survival risks by race was observed in the 3 studies that compared men of African ancestry vs Caucasian (HR: 1.09 [0.77, 1.53], 0.68 [0.36, 1.29] and 1.05 [0.97, 1.14]). HRs of 0.90 [0.52, 1.57] and 0.76 [0.61, 0.95] were reported in the 2 studies comparing OS in men of African ancestry vs non-African ancestry. No studies reported a significant increased risk of death by race. Conclusions: Overall, men of African ancestry were largely underrepresented in MPC clinical trials. Concerted efforts are needed to increase the enrollment of this at-risk population in future clinical trial programs. Additional studies are needed to confirm the absence of differences in survival by race in real-life settings.

5062 Background: There is a lack of data on the incidence rates (IRs) and racial differences in advanced prostate cancer (PC) clinical states. This is the first study to evaluate PC IRs among Black and White men in the Veterans Affairs Healthcare System (VAHCS) in the following clinical states: non-metastatic hormone-sensitive PC (nmHSPC); de novo metastatic HSPC (mHSPC); non-metastatic castration-resistant PC (nmCRPC); metastatic CRPC (mCRPC). Methods: This retrospective cohort study included adult Black and White men who were active users of the VAHCS, having ≥ two visits at VA centers over any 18-month interval during the study period (2012-2019). PC was identified by ≥ two ICD codes for PC on separate dates. Metastatic status was identified by an algorithm of ICD codes and common treatments for metastatic PC. Castrate resistant status was determined based on rising PSA during periods of continuous androgen deprivation therapy. Annual IRs for each clinical state and rate ratios (RR) for race were standardized using age and race-specific population estimates from the U.S. Census. The joinpoint regression software 4.9.0.0 was used to evaluate trends and identify change points in IRs over time. Results: 2019 IRs (per 100K person-years) and 95% confidence intervals among Black and White men respectively by clinical state were 453.0 (441.2, 464.7) and 205.3 (201.5, 209.1) (nmHSPC); 33.7 (30.4, 37.0) and 15.1 (14.1, 16.0) (mHSPC); 23.4 (21.0, 25.9) and 8.5 (7.8, 9.1) (nmCRPC); and 49.1 (45.5, 52.8) and 19.4 (18.4, 20.3) (mCRPC). The RR for all clinical states was significantly higher for Black vs. White men (all p < 0.0001): 2.2 (nmHSPC and mHSPC), 2.8 (nmCRPC), and 2.5 (mCRPC). Although IRs varied over time, these RRs were consistent across time. Trends in IRs over time were also consistent by race. From 2012, the IRs for nmHSPC declined to a nadir in 2016 (annual percent change (APC) -9.1%) and then increased through 2019 (APC = 3.1%). IRs for mHSPC increased throughout the study period (APC = 10.6%). IRs for nmCRPC decreased from 2012 to a nadir in 2014 (APC = -9.3%) and then increased through 2019 (APC = 3.8%). IRs for mCRPC increased from 2012 to 2016 (APC = 7.7%) and then leveled off through 2019 (APC = -0.2%). Conclusions: Our findings provide novel and comprehensive data on IRs across prostate cancer clinical states by race and over time within the VAHCS. Despite the VAHCS providing an environment of relatively equal access to care, Black men experience a disproportionate burden of PC with IRs over 2-fold higher for all clinical states relative to White men. This highlights that resolving access to care alone is unlikely to fully eliminate PC racial differences and that there are other multifactorial issues to address. The temporal trends for nmHSPC observed in our study, including the nadir in 2016, are consistent with the timing of the 2012 US Preventive Services Task Force guidelines advising against PSA screening and the subsequent draft reversal in 2017.

63 Background: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease with significant morbidity. Poly adenosine diphosphate-ribose polymerase inhibitors (PARPi) are targeted therapeutics approved to treat mCRPC patients with genetic mutations in homologous recombination repair (HRR). However, to benefit from PARPi as a single agent, patients usually need to undergo biomarker testing to determine their mutation status. As an initial step to understand patient preferences for mCRPC treatments, this study investigated the treatment features important to mCRPC patients and their preferences for and perceptions of biomarker testing. Methods: This preliminary qualitative study included 25 men in the US, UK, Germany, Spain, and Japan with self-reported mCRPC diagnosed at least 6 months previously. Participants completed a 60-minute one-on-one interview about mCRPC treatments and disease impact. Results: Participants had a mean age of 62 years and were diagnosed with prostate cancer an average of 68 months prior. About half (52%) had metastasized > 1 year prior and more than half (56%) reported no HRR genetic mutation . The most frequently reported symptoms were pain (60%), urinary problems (56%), and fatigue (32%). Participants stated that pain impacted their sleep, daily activities, and social lives. 60% reported they shared treatment decision-making with their physician, some (24%) shared it with partners or caregivers, and others (32%) left treatment decisions up to their physician due to their lack of knowledge. Quality of life (QoL) was the most important treatment benefit reported (56%), followed by progression-free survival (PFS) (52%), overall survival (OS) (48%), and reduced pain (44%). Some participants reported their desire for prolonged survival needed to be balanced with adequate QoL. Few participants reported reduced fatigue (24%) or urinary problems (12%) as desired treatment benefits. 64% had previously undergone biomarker testing to determine mutation status. 56% of tested participants reported that their physician discussed the purpose and benefits of testing. Based on conversations with their physicians, both tested and untested participants felt that biomarker testing would inform them about heritable risk of mutation and help find new targeted treatments. Untested participants with a negative view of biomarker testing (22%) reported concerns about the need for further invasive biopsies. Conclusions: QoL followed by PFS, OS, and reduced pain were the most important benefits of treatment to participants. More than half of participants had a positive view of biomarker testing, especially if testing could lead to targeted therapies and inform about heritable risk. These results will inform the design of an international discrete choice study of biomarker testing among men with mCRPC.

49 Background: mCRPC is an incurable disease with poor prognosis. Though multiple treatments such as novel hormonal therapies (NHT: abiraterone [abi], enzalutamide [enza], docetaxel [doce], cabazitaxel [caba], sipuleucel-T [Sip-T] etc.) are approved, real-world data regarding treatment sequencing are lacking. This study assesses the real-world treatment patterns within the context of FDA-approved life-prolonging treatments for mCRPC. Methods: The IBM MarketScan database was used to identify newly diagnosed (incident) mCRPC patients from 1/1/2014-5/31/2020. Adult males were required to have a diagnosis of PC, and subsequently evidence of metastasis and castration (medical or surgical). Incident mCRPC status (index) was determined 3 ways: 1) treatment with an NHT within 3 months after castration and an FDA-approved mCRPC treatment ≥3 months after NHT; 2) first FDA-approved treatment ≥6 months after castration; 3) first FDA-approved treatment 3-6 months after castration and a second FDA-approved treatment ≥3 months after treatment. Lines of therapy (LOT) were measured in the variable-length follow-up of ≥1 month and consisted of all drugs observed within 28 days of first observed treatment. Duration of therapy was measured as start of line to start of next line or end of enrollment. Results: A total of 2,912 mCRPC patients met all study criteria and received ≥1 LOT. Among those, 48.7% had ≥2 LOT, and 21.8% had ≥3 LOT. Patients were an average age of 71 years at index and used leuprolide (87%), abi (10%), doce (9%) and enza (8%) prior to index. In mCRPC the most common observed first line (1L) monotherapy regimens were abi (35%), enza (34%), and doce (14%). The most common observed second-line (2L) treatments were enza (36%), abi (27%), and doce (14%). Mean duration of 1L was 292 days compared to 245 days in 2L. The most frequently observed treatment sequences (1L to 2L) are reported in the table. Opioids (62%) and denosumab (47%) use was common in mCRPC patients. Conclusions: Among mCRPC patients, NHTs were the most common 1st and 2nd LOTs and alternate NHT after a first NHT was the most common sequence. With rapidly evolving treatment options in metastatic prostate cancer, these data can help guide estimation of eligible patients for different clinical trials. Further studies are needed to understand the high attrition from 1L to subsequent lines of therapy, the reasons for treatment preference and impact on clinical outcomes with different treatment sequencings.[Table: see text]

49 Background: In May 2020, Olaparib was approved for HRRm mCRPC post progression on abiraterone and enzalutamide, and rucaparib was approved for BRCAm mCPRC following progression on androgen receptor targeted inhibitors and prior taxane therapy for mCRPC. HRRm are associated with approximately 25% of mCRPC and may be derived from germline or somatic origin. Somatic and germline alterations can be detected by tumour testing, but to differentiate between these, independent germline testing is needed. This study examined real-world genomic/genetic testing (GT) patterns in patients (pts) diagnosed with mCRPC in the United States (US). Methods: Data were drawn from the Adelphi Prostate Cancer Disease Specific Programme; a point-in-time survey administered to oncologists (onc), urologists (uro) and surgeons (sur) between January and August 2020 in the US. Physicians (phys) completed an attitudinal survey and a patient record form for the next four to nine mCRPC pts seen. Study variables included patient demographics, clinical factors and GT patterns. HRRm testers were defined as phys who tested for HRRm. Pts were identified as positive, negative or unknown depending on the outcome of the HRRm test. Results: A total of 72 phys (69% onc/ 29% uro/ 1% sur; 40% academic vs. 60% community) reported on 346 mCRPC pts. 41% of phys were based in the Northeast, 24% Midwest, 23% South and 13% in the West region of the US. 65 phys (90%) reported having access to overall GT; of these 5% identified as having access to germline tests only, while 94% were able to test for germline and somatic mutations. Challenges to conducting GT overall were ‘cost per test’ (50%), ‘having to send out for the tests (within country)’ (25%), ‘inadequate sample available’ (25%) and ‘patient refusal’ (25%). GT was typically conducted at identification of castrate-resistance (52%), metastases (51%) and at initial diagnosis (49%). 72% of total phys were HRRm testers; for these, patient characteristics primarily driving HRRm testing included Ashkenazi Jewish heritage (63%) and ECOG of 2-4 (58%). Other common drivers were family history, young diagnosis age and hormone therapy failure (all 46%). 132 (38% of 326) mCRPC pts were tested for HRRm; 39% of tested pts were identified with a HRRm. Most common HRRm tested were BRCA1 (90%), BRCA2 (89%) and ATM (55%). Conclusions: In this study majority of US phys had access to GT, but testing was only performed in 38% of pts with mCRPC. The higher than expected % of pts identified with an HRRm suggest that molecular testing was prioritised in high risk populations, as identified by the phys. With the recent approval of olaparib and rucaparib, GT may become more routine in clinical practice to identify eligible pts. Broader testing may also depend on addressing other barriers to testing including cost and testing logistics/practicalities.