Nordblad, Blake

5076 Background: C and Lu are both life-prolonging therapies for pts with mCRPC after progression on androgen receptor pathway inhibitor (ARPI) and docetaxel (D). Herein, our objective was to assess the comparative effectiveness of C vs. Lu in pts with mCRPC with prior progression on D and ARPI in real-world pts in the USA. Methods: A de-identified nationwide Flatiron Health electronic health record (EHR)-derived database was used to extract pt-level data. Eligibility: pts with mCRPC who progressed on D and ARPI and received for the first-time single-agent C or Lu. Pts who received alternative Lu or C in a later line of therapy (LOT) were excluded. Endpoints: real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS). These were summarized via Kaplan-Meier survival estimates with a 95% confidence interval (CI) and compared in the context of propensity score (PS) matching weighted analysis using the Cox proportional hazard model. PS model included the following covariates: age, race-ethnicity, socioeconomic status, treatment year, Gleason score, ECOG performance status, log2PSA, alkaline phosphatase, hemoglobin, creatinine, LOT, insurance, and practice type. All the covariates achieved balance after PS matching weighting. Results: Among 24,105 pts with metastatic prostate cancer in the dataset, 1,445 met the eligibility criteria and were included (1,227 treated with C, 218 treated with Lu). In C cohort: median age was 73 (IQR 67 – 78), 66.9% had Gleason score ≥ 8, and median LOT was 4 (IQR 3-4). In Lu cohort: median age was 75 (IQR 67.25 – 80), 68.1% had Gleason score ≥ 8, and median LOT was 4 (IQR 3-5). In PS matching weighting analysis, there was evidence that pts receiving Lu had a significantly improved rwTTNT (median 8.3 months [mo], 95% CI 6.3 – 9.8) compared to those receiving C (median 4.7 mo, 95% CI 4.2 – 5.4) (HR 0.49, 95% CI 0.37 – 0.63, p < 0.001), which persisted after adjusting for covariates (HR 0.43, 95% CI 0.32 – 0.57, p < 0.001). Additionally, there was evidence that rwOS was longer in pts receiving Lu (median 10.3, 95% CI 8.9 – 12.8) compared to those receiving C (median 8.8 mo, 95% CI 6.6 – 10.8) (HR 0.69, 95% CI 0.51 – 0.92, p = 0.01). This improvement in rwOS with Lu compared to C persisted after adjusting for covariates (HR 0.61, 95% CI 0.44 – 0.84, p < 0.001). Conclusions: This is the largest real-world data to date assessing the comparative effectiveness of Lu vs. C, and it showed significantly longer rwTTNT and rwOS with Lu compared to C in pts with mCRPC pretreated with ARPI and D. Limitations: retrospective nature, selection bias, missingness, lack of randomization, etc. and residual confounding in real-world datasets. Upon external validation, these findings could guide treatment selection in the clinic and design of clinical trials.

727 Background: Despite the availability of targeted therapies like erdafitinib for pts with aUC with susceptible genomic alterations, the rate of NGS testing remains low at 32% in the United States (Hage Chehade...Swami, JAMA Network Open, 2024). Furthermore, limited data exist regarding the timing of NGS testing in relation to the time of death. Herein, we sought to assess the rates of NGS testing at the end of life in pts with aUC in a real-world patient population. Methods: A de-identified nationwide Flatiron Health electronic health record (EHR)-derived database was used to extract patient-level data. Inclusion criteria: pts who received NGS testing (blood/tissue) and who had a date of death recorded. The analytic cohort included pts diagnosed with aUC between 1/1/2011 and 11/14/2022 who received first NGS testing results between 5/3/2012 and 12/21/2022. The time difference between each pt’s first NGS result delivered and death was calculated, and thereafter, pts were categorized into 3 categories: pts receiving results > 3 months (mo) before death, within 3 mo of death, or after death. The frequency and percentages of the 3 categories were reported, as well as by year of death. The percentages in each category were compared between 2019 (year of erdafitinib approval) and 2022 (last year in dataset) to evaluate changes in NGS testing trend. Results: Among 12,157 pts with aUC in the dataset, 1,637 had both a recorded date of death and underwent NGS testing, and were eligible and included in final analysis. The median age was 72 (IQR 66 – 79). The majority were male (73%), White non-Hispanic (76%), and treated in community practice (86%). 68.2% received NGS results > 3 mo before death (n = 1,117), 28.3% received results within 3 mo of death (n = 464), and 3.4% of NGS results were reported after death (n = 56). In pts who died in 2019 versus 2022, the percentage of pts receiving NGS results > 3 mo before death increased from 61% to 75%, while the percentage of pts receiving results within 3 months decreased from 33% to 22%, and the percentage of NGS results reported after death declined from 5.2 to 2.7%. Baseline characteristics (including race-ethnicity, insurance plan, practice type [academic vs. community]) in these categories will be presented at the meeting. Conclusions: Our findings suggest that a sizeable number of pts with aUC (∼ 32%) received their first NGS testing results towards the end of life, highlighting the need to integrate genomic testing earlier during the course of the disease to optimize benefit with targeted therapies. These results could inform clinical practice and therapeutic decisions in the clinic. CHC, YJ: Equal contribution; US, NA: Senior authors.

75 Background: The Rx landscape of pts with mCRPC has recently evolved with the approval of lutetium-177-PSMA-617 (Lu-177) and poly(ADP) ribose polymerase inhibitors (PARPi) either as single agents or as combinations with an androgen receptor pathway inhibitor (ARPI) [PMID: 37442702]. However, real-world data on the uptake of these agents are lacking. Herein, we sought to assess the Rx patterns and attrition rates of pts with mCRPC in the era of newly approved therapies. Methods: The de-identified nationwide Flatiron Health Electronic-Health Record (EHR)-derived database was used to extract pt-level data. Eligibility criteria: diagnosis of mCRPC and Rx line (L) information. The data cut-off date was 5/31/2024. Rx patterns in each line of therapies were summarized using frequency and percentages. All analysis was done using R version 4.2.3. Results: Of the overall cohort of 24,105 pts with metastatic prostate cancer, 12,333 pts diagnosed with mCRPC between 1/1/2013 and 5/9/2024 met the eligibility criteria and were included. Rx trends are summarized (Table). Of pts receiving 1L Rx, 61% of pts received 2L therapy, and 35% received 3L therapy. Androgen receptor pathway inhibitor (ARPI) was the most common Rx in the 1L setting (73.7%), followed by taxane (10%) and sipuleucel-T (3.8%). In 2L, ARPI was again the most frequent Rx (46.8%), followed by taxane (23.6%). In 3L, taxane became the most frequent Rx (35.4%), followed by ARPI (26.2%) and radium-223 (4.9%). Rx trends per year will be presented in the meeting. Conclusions: In the current era,a high proportion of pts with mCRPC receiving 1L Rx do not receive a subsequent line of Rx (39% of pts do not receive 2L, and 65% do not receive 3L Rx). ARPIs and taxanes remain the most frequently used Rx options in most L of therapy. These findings highlight the need for better tolerated Rx, therapies with a novel mechanism of action, and improved access to care for our pts. Rx trends per year will be presented in the meeting. Rx patterns in pts with mCRPC. Rx 1L, n (%)N = 12,333 2L, n (%)N = 7475 3L, n (%)N = 4316 4L, n (%)N = 2339 5L, n (%)N = 1225 ARPI 9085 (73.7) 3503 (46.8) 1130 (26.2) 356 (15.2) 157 (12.8) PARPi-based therapies 93 (0.8) 185 (2.5) 142 (3.3) 98 (4.2) 47 (3.9) Platinum-based therapy 127 (1) 216 (2.9) 198 (4.6) 148 (6.3) 130 (10.6) Lu-177-based therapies 50 (0.4) 109 (1.5) 169 (3.9) 143 (6.3) 103 (8.4) Radium-223 183 (1.5) 241 (3.2) 213 (4.9) 125 (5.3) 79 (6.4) Sipuleucel-T 474 (3.8) 94 (1.3) 53 (1.2) 18 (0.8) 8 (0.7) Taxane 1240 (10) 1763 (23.6) 1526 (35.4) 935 (40) 393 (32) Pembrolizumab 24 (0.2) 41 (0.5) 36 (0.8) 27 (1.2) 29 (2.4) Other*/not-applicable** 665 (5.4)/392 (3.2) 1000 (13.4)/323 (4.3) 602 (14)/247 (5.7) 320 (13.7)/169 (7.2) 162 (13.3)/117 (9.5) *Includes drugs approved for mCRPC in combination with unapproved agents or clinical trial drugs. **Includes agents not approved for prostate cancer.

90 Background: Poly(ADP) ribose polymerase inhibitors and pembrolizumab are approved for patients with metastatic prostate cancer (mPC) with susceptible genomic alterations based on NGS testing. We recently reported that the rate of NGS testing in mPC remains low at 29.3% in the United States (1). Herein, we investigated the rates of NGS testing at the end of life in a real-world patient population. Methods: This study utilized the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Eligibility: diagnosis of mPC, with information on receipt of NGS testing (blood/tissue) and recorded date of death. The time between each patient’s first NGS testing result date and date of death was measured and categorized into 3 groups: NGS test results delivered more than 3 months (mo) before death, within 3 mo of death, and delivered after death. Frequencies and percentages of these 3 categories were reported, also by the year of death. Results: Out of 24,105 patients with mPC in the database, 3,397 had both a recorded date of death and underwent NGS testing and were eligible and included. The median age was 74 (IQR 67–80), 70% were White non-Hispanic, and 83% were treated in a community-based practice. In these patients, 2,901 (85.4%) NGS results were reported more than 3 mo before death, 457 (13.5%) within 3 mo of death, and 39 (1.1%) after death. From 2015 to 2024, the percentage of patients receiving their result more than 3 mo before death increased from 27% to 91%, while those receiving it within 3 mo before death decreased from 55% to 8.5%, and the percentage of NGS results reported after death declined from 18% to 0.6%. Baseline characteristics (including race-ethnicity, insurance plan, practice type [academic vs. community]) in these categories will be presented at the meeting. Conclusions: Despite the availability of life-prolonging targeted therapies based on NGS testing results for patients with mPC, in ∼14% of patients, the first NGS testing results were reported within 3 mo before death or after death. The lack of timely NGS testing limits patients' access to life-prolonging personalized treatments in earlier settings, resulting in missed opportunities for improved outcomes. 1. Hage Chehade, Swami, JAMA Network Open, 2024.

109 Background: C and Lu are associated with overall survival benefit and approved for pts with mCRPC after prior treatment with docetaxel and an androgen receptor pathway inhibitor (ARPI). However, in real-world settings, administering Lu requires coordination across specialties and resources [PMID: 36637862], which could delay its administration. Herein, we sought to compare the time from medication order to administering the first dose of C versus Lu. Methods: This study used pt level data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Inclusion criteria: availability of the date of the first order of single-agent C or Lu and the date of first administration of the drugs. The time between the first medication order to the administration of single-agent C or Lu was measured. Wilcoxon rank-sum test was used to compare the median days between medication order to administration between these 2 agents and a stratified analysis by practice type and insurance was performed. Results: Of 2,329 orders, 2,045 orders were for C between 1/1/2013 and 1/26/2024, while 284 were for Lu between 8/1/2013 and 12/6/2023. The time from medication order to administration was significantly longer with Lu (median 22 days, IQR 12-43) compared to C (median 7 days, IQR 3-14, p < 0.001). Time from medication order to administration of C and Lu by practice type and insurance is summarized (Table). At the time of the first order, pts in Lu cohort, compared to C cohort, were significantly older (median age 74 vs. 72, p < 0.001), more likely to be treated at an academic practice (27% vs. 15%, p < 0.001), and more likely to be covered by a commercial health plan (80% vs. 73%, p < 0.001). Conclusions: Our results show that it takes significantly longer to administer Lu compared to C across different practice types and most insurance plans. These results could inform healthcare policies aimed at improving access to Lu and guide treatment selection in the clinic. Time from medication order to administration of C and Lu by practice type and insurance. Category Subtype (number of orders for C/number of orders for Lu) CN = 2045 LuN = 284 p-value Practice type, mean (range) (days) Academic (315/77) 1.3 (0 – 59) 9.2 (0 – 55) < 0.001 Community (1730/207) 13 (0 – 243) 44 (1 – 282) < 0.001 Insurance, mean (range) (days) Commercial (1494/226) 11 (0 – 163) 32 (0 – 215) < 0.001 Medicare/other government programs (266/46) 10 (0 – 120) 46 (0 – 282) < 0.001 Medicaid (32/2) 9 (0 – 76) 28 (0 – 55) 0.8 Others (72/6) 12 (0 – 42) 21 (0 – 41) 0.2 Unknown (181/4) 14 (0 – 243) 76 (39 – 91) < 0.001