Prostate-specific antigen response among Black and non-Black patients with advanced prostate cancer treated with apalutamide in a urology setting.

124 Background: Apalutamide (APA) is approved to treat patients with non-metastatic castration-resistant prostate cancer (nmCRPC) or metastatic castration-sensitive prostate cancer (mCSPC) in the United States (US) but low enrollment of Black patients in clinical trials has led to limited clinical data about APA for this population. This study describes prostate-specific antigen (PSA) responses among Black and non-Black patients with nmCRPC or mCSPC treated with APA in a real-world community urology setting. Methods: Clinical data from 2/2018 to 3/2021 collected at 69 US urology practices were used to evaluate nmCRPC or mCSPC patients who received ≥1 APA prescription fill (index date). Baseline PSA was reported based with the most recent baseline PSA value and PSA doubling time (PSADT) in months (mo) was calculated in patients with at least 2 PSA tests before APA initiation. PSA response defined as the proportion of patients achieving either a reduction of 50% (PSA50) or 90% (PSA90) from baseline and was evaluated in patients with a PSA test result 8 weeks or later after initiating APA. Among patients with a response, the time from the index date to the response was also evaluated. Study results for Black and non-Black cohorts were summarized separately. Results: Data from 289 nmCRPC (19% Black) and 237 mCSPC (19% Black) patients were identified. Median baseline PSA, median baseline PSADT and post-index PSA responses are shown in Table. A PSA50 response was attained by numerically similar proportions of Black and non-Black patients with nmCRPC or mCSPC. A PSA90 response was observed in a numerically higher proportion of Black than non-Black nmCRPC patients. Median time to PSA50 and PSA90 was also similar between groups. Conclusions: This real-world study of nmCRPC and mCSPC patients demonstrates that PSA50 and PSA90 responses are achieved by high proportions of both Black and non-Black patients. Moreover, the PSA50 and PSA90 responses observed in this study are highly consistent with those observed in APA’s Phase 3 registrational trials for nmCRPC (SPARTAN)1 and for mCSPC (TITAN)2. References: 1Smith MR, et al. N Engl J Med. 2018;378:1408-1418. 2Chi KN, et al. N Engl J Med. 2019;381:13-24. Funding Source: Janssen Scientific Affairs, LLC.[Table: see text]

Feasibility and safety of targeted focal microwave ablation of the index tumor in patients with low to intermediate risk prostate cancer: Results of the FOSTINE trial

Objective To assess the feasibility, safety and precision of organ-based tracking (OBT)-fusion targeted focal microwave ablation (FMA), in patients with low to intermediate risk prostate cancer. Patients and method Ten patients with a visible index tumor of Gleason score ≤3+4, largest diameter <20mm were included. Transrectal OBT-fusion targeted FMA was performed using an 18G needle. Primary endpoint was the evidence of complete overlap of the index tumor by ablation zone necrosis on MRI 7 days after ablation. Urinary and sexual function were assessed with IPSS, IIEF5 and MSHQ-EjD-SF. Oncological outcomes were assessed with PSA at 2 and 6 months, and re-biopsy at 6 months. Results Median [IQR] age was 64.5 [61–72] years and baseline PSA was 5 [4.3–8.1] ng/mL. Seven (70%) and 3 (30%) patients had a low and intermediate risk cancer, respectively. Median largest tumor axis was of 11 [9.0–15.0] mm. Median duration of procedure was of 82 [44–170] min. No patient reported any pain or rectal bleeding, and all 10 patients were discharged the next day. Seven days after ablation, total necrosis of the index tumor on MRI was obtained in eight (80% [95%CI 55%-100%]) patients. One patient was treated with radical prostatectomy. Re-biopsy at 6 months in the other 9 did not show evidence of cancer in 4 patients. IPSS, IIEF-5 and MSHQ-EjD-SF were not statistically different between baseline and 6 months follow up. Conclusions OBT-fusion targeted FMA was feasible, precise, and safe in patients with low to intermediate risk localized prostate cancer.

A phase I/II study of hydroxychloroquine and suba-itraconazole in men with biochemical relapse of prostate cancer (HITMAN-PC): Dose escalation results.

114 Background: Preclinical data show hydroxychloroquine (HCQ) and suba-itraconazole (SI) together enhance prostate cancer cell death. The proposed mechanism is lysosome dysfunction including sequestration of cholesterol in endosomes and inhibition of gogi-lyosome trafficking. HCQ/SI could delay androgen deprivation therapy (ADT) and its associated morbidity in men with biochemical relapse of prostate cancer. In this phase I/II study, maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of HCQ/SI was investigated in such patients. Methods: Patients received escalating doses of HCQ with fixed SI 150mg BD in rolling 6 design. This will be followed by a planned phase II Simon 2-stage cohort expansion. Results: Eleven men were treated with HCQ/SI. Median age 73 (range 69-77), baseline PSA 4.4 µg/L (1.6-22.4) and doubling time 5.3 months (3.3-15.3). Two experienced dose-limiting toxicity: grade 3 diarrhoea and grade 3 alanine transferase elevation, both at HCQ 600mg BD. Most common treatment-related adverse events (AEs) were hypertension (91% all grade/18% grade 3), QTc prolongation (55%/0%), diarrhoea (36%/9%), and nausea (36%/0%). There were no grade 4 AEs or deaths. While there were no PSA responses (≥50% fall from baseline), PSA PFS by PCWG3 criteria was 5.5 months (2.0-9.0), and PSA doubling time was prolonged at 4 and 12 weeks in 82% and 45% respectively. ADT-free and metastasis-free survival are 14.3 months (95% CI 4.9-23.8) and 15.9 months (95% CI unevaluable) respectively. PK data will be presented. Conclusions: HCQ/SI demonstrated acceptable safety with MTD 600mg BD and RP2D 400mg BD. There is early signal of activity and phase II enrolment is to begin. Clinical trial information: NCT03513211.

Prostate-specific antigen (PSA) kinetics in patients (pts) with advanced prostate cancer treated with apalutamide: Results from the TITAN and SPARTAN studies.

5541 Background: The phase III TITAN and SPARTAN studies demonstrated improved outcomes with the addition of apalutamide (APA) to androgen deprivation therapy (ADT); outcomes included prolonging overall survival and radiographic progression-free survival (rPFS) in metastatic castration-sensitive prostate cancer (mCSPC) in TITAN, and metastasis-free survival (MFS) in nonmetastatic castration-resistant PC (nmCRPC) in SPARTAN. A post hoc analysis of PSA kinetics in pts from both studies is reported. Methods: Baseline PSA at randomization, time to PSA nadir, and proportion of pts achieving a PSA decline of ≥ 90% (PSA90) and of pts achieving a PSA ≤ 0.2 ng/mL at 3 and 12 months and at any time after treatment in the APA arms of the TITAN and SPARTAN studies were evaluated. Within each study, rPFS/MFS were compared between pts achieving a PSA90 or PSA ≤ 0.2 ng/mL response vs not. Results: 525 TITAN pts and 806 SPARTAN pts treated with APA were included in the analysis. Median baseline PSA, time to PSA nadir, median PSA nadir, and maximum percentage changes from baseline PSA are shown in the table. PSA90 and confirmed PSA ≤ 0.2 ng/mL were evident as early as 3 months in both TITAN and SPARTAN, and percentage of confirmed response continued to increase at 12 months. Pts treated with APA who achieved PSA90 were at lower risk of rPFS events in TITAN and of MFS events in SPARTAN, with a hazard ratio (95% confidence interval) of 0.46 (0.321-0.653) and 0.36 (0.271-0.489) in each respective study (both p < 0.0001), compared with APA pts who did not achieve PSA90. Pts with confirmed PSA ≤ 0.2 ng/mL had similar rPFS and MFS benefits. Conclusions: Pts with advanced PC, whether mCSPC or nmCRPC, treated with APA + ADT demonstrated rapid PSA declines that continued over time. There was a high rate of pts with PSA90 and with PSA ≤ 0.2 ng/mL responses, with a majority of pts reaching PSA90 by 12 months. Pts achieving PSA90 and/or PSA nadir of ≤ 0.2 ng/mL had a prolonged rPFS and MFS in TITAN and SPARTAN, respectively. Clinical trial information: NCT02489318; NCT01946204 . [Table: see text]

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: Results of cohort 6 of the COSMIC-021 study.

5564 Background: Cabozantinib (C) may enhance response to immune checkpoint inhibitors (ICIs) by promoting an immune-permissive microenvironment and has shown encouraging activity in combination with ICIs in tumor types including RCC and HCC. C and atezolizumab (A) have shown low objective response rates as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) (Smith JCO 2012; Kim JCO 2018). COSMIC-021 (NCT03170960), a multinational phase 1b study, is evaluating the combination of C + A in various solid tumors. We report results for Cohort 6 in mCRPC. Methods: Eligible patients (pts) were required to have radiographic progression in soft tissue after enzalutamide and/or abiraterone, measurable disease, and an ECOG PS of 0 or 1. Prior chemotherapy for mCSPC was permitted. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for the first year and Q12W thereafter. The primary endpoint is ORR per RECIST 1.1. Other endpoints include safety, ORR per irRECIST, duration of response (DOR), PFS, and OS. Results are presented for the first 44 pts enrolled. Results: Median follow-up as of Dec 20, 2019 was 12.6 mo (range 5, 20) for the 44 mCRPC pts. Median age was 70 y (range 49, 90), 50% had ECOG PS 1, 34% had visceral metastases, and 61% had extrapelvic lymph node metastases. 27% had prior docetaxel and 52% had 2 prior novel hormonal therapies. The most common any grade treatment-related adverse events (TRAEs) were fatigue (50%), nausea (43%), decreased appetite (39%), diarrhea (39%), dysgeusia (34%), and PPE (32%). One grade 5 TRAE of dehydration was reported in a 90 y/o. Median duration of treatment was 6.3 mo. ORR per RECIST 1.1 among all 44 pts was 32% (2 CRs [4.5%] and 12 PRs [27%]); 21 (48%) pts had SD resulting in a disease control rate of 80% in all pts. One pt with PD per RECIST 1.1 had an irPR per irRECIST. ORR per RECIST 1.1 was 33% in 36 pts with high-risk disease (visceral and/or extrapelvic lymph node metastases). Median DOR for all pts with response per RECIST 1.1 was 8.3 mo (range 2.8, 9.8+). 17 (50%) of 34 pts with post-baseline PSA evaluation had a decrease in PSA. In 12 responders with post-baseline PSA evaluation, 8 (67%) had a PSA decrease ≥50%. Tumor PD-L1 expression will also be reported. Conclusions: The combination of C + A had a tolerable safety profile and demonstrated clinically meaningful activity with durable responses in men with mCRPC. Given the encouraging activity in these pts, especially in those with high-risk disease, further evaluation of C + A in men with mCRPC is being pursued. Clinical trial information: NCT03170960 .

Real-world analysis of prostate-specific antigen (PSA) outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide (ENZA).

33 Background: ENZA showed efficacy in chemotherapy-naïve men with mCRPC in a clinical trial setting (PREVAIL). We report real-world outcomes with ENZA for this population in a urology practice setting. Methods: This retrospective cohort study included men with prostate cancer newly initiating ENZA in the IntrinsiQ Specialty Solutions™ urology electronic medical records database between September 1, 2014 and February 28, 2018. Due to the approved indication in the study time frame, prescription of ENZA (first claim date = index date) was used as a proxy for mCRPC. Patients with evidence of prior chemotherapy and/or abiraterone were excluded. PSA value closest to index date (±30 days) was used as baseline. Men were followed until the earliest of: discontinuing ENZA, leaving practice, death, or study end. Best PSA response (largest decline or smallest increase in absence of decline from baseline), PSA declines of ≥50% and ≥90%, undetectable PSA, and time to PSA progression were analyzed. Results: We identified 931 eligible men. Most (>95%) were ≥60 years old; hypertension (54.6%) and diabetes (17.0%) were the most common comorbidities. Median (interquartile range [IQR]) baseline PSA was 9.0 (2, 37) ng/dL. Median (IQR) follow-up time was 12.5 (7.6, 19.4) months, during which a median (IQR) of 4 (3, 6) PSA tests were observed. Median time between two adjacent PSA tests was 2.0 months. A ≥50% and ≥90% PSA decline was observed in 55.0% and 23.8%, respectively. Best PSA response was a median (IQR) PSA decline of 58% (-89%, 1%), with 14.2% reaching an undetectable PSA value. Median time to PSA progression was 18.5 months (95% confidence interval 15.6, 23.7). Conclusions: This real-world study supports the effectiveness of ENZA in patients with mCRPC. The median PSA at treatment was much lower than PREVAIL, potentially explaining the longer time to PSA progression vs. PREVAIL. However, a lower proportion had PSA declines of ≥50% and ≥90% vs. PREVAIL, which may be attributed to more frequent PSA monitoring within a clinical trial setting and thus more opportunity to capture the true best PSA response.

Prognostic factors that affect survival outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223.

225 Background: Radium-223 (Ra-223) improved overall survival (OS) in men with mCRPC with predominantly bone metastases. We analyzed their survival outcomes to identify factors associated with prognosis for men treated with Ra-223. Methods: This was a retrospective study of men with mCRPC at Princess Margaret Cancer Centre treated with Ra-223. Demographics, disease characteristics, number of bone metastasis [ < 6, 6-20, > 20], laboratory results, number of Ra-223 doses, systemic treatment lines after radium-223, use of bone protecting agents (BPA) and survival outcomes were collected. OS and progression-free survival (PFS) were estimated by Kaplan-Meier (log-rank) analysis. Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) were used to evaluate patient and disease characteristics, number of Ra-223 doses and overall survival. Results: 114 men received Ra-223 between May 2015 and May 2018 with median age 75 years (range 53-93). Median radium doses was 5 (68 [59.6%] received > 4 doses, 46 [40.4%] received ≤4 doses). Median baseline ALP 113.5 U/L (31-1121), median baseline Hb 118 g/L (69-153), median baseline PSA 70.2 ug/L (0.15-5275), median LDH 242 UL (82-1426). 58% had 6-20 bone metastases and 28% had > 20 bone metastases. The median OS and PFS for men who received ≤4 doses vs > 4 doses was 4.56 vs 19.8 months (HR = 8.4; 95%CI: 4.861-14.62; p≤ 0.0001) and 2.9 vs 7.45 months (HR = 4.6; 95%CI: 2.837 to 7.537; p≤ 0.0001) respectively. The baseline median ALP was (154 vs 98; p = 0.03) for men who received ≤4 doses vs > 4 doses Ra-223. On UVA, ECOG 0-1 (HR = 0.33; p = 0.0003), baseline PSA < 70 ug/L (HR = 0.51; p = 0.0023), LDH < 250 U/L (HR 0.55; p = 0.0082), Hb > 120 g/L(HR 0.46; p = 0.0004), ALP < 150 U/l(HR 0.38; p ≤ 0.0001) and receipt of subsequent treatment after Ra-223 (HR = 0.33; p < 0.0001) were associated with improved OS. On MVA, receipt of subsequent treatment, administration > 4 cycles of Ra-223 and baseline ALP < 150 U/L were associated with improved OS. Conclusions: Men who receive > 4 cycles of Ra-223 have significantly better OS than those who receive ≤4 doses. Baseline ALP was independently associated with better OS and could be used to identify patients most likely to benefit from Ra-223.

The relation between baseline PSA and symptomatic progression in Egyptian BPH patients receiving tamsulosin monotherapy: an exploratory multicentric prospective study

Background To examine the relation of baseline serum prostatic-specific antigen (PSA) to symptomatic changes in men with benign prostatic hyperplasia (BPH) receiving tamsulosin through its relation to changes in international prostate symptom score (IPSS) and maximum urinary flow rate (Qmax) and the occurrence of acute urine retention (AUR). Results We conducted a multicentric prospective cohort study. BPH patients were included from May 2015 till January 2018. We collected IPSS recording, prostate volume (PV) Qmax. After 2 years of medical treatment with tamsulosin 0.4 mg once daily, full initial evaluation was repeated for all patients. Improvement in IPSS and Qmax was recorded and compared to initial PSA levels. Follow-up was aborted for patients who developed AUR. Moreover, the data of AUR patients were recorded and compared to initial PSA levels. The study included 437 Egyptian patients, and 414 patients (94.7%) had symptomatic improvement through the 2 years of follow-up on tamsulosin monotherapy. In total, 23 patients (5.3%) developed AUR during follow-up. There was a significant association between AUR and higher baseline PSA level (p < 0.001). On the other hand, statistical analysis showed that there was no significant correlation between baseline serum PSA and the improvement in IPSS (r = − 0.02, p = 0.684) or Qmax (r = − 0.06, p = 0.267). The multivariate analysis showed that baseline PSA and PV were independent predictors for AUR (p < 0.001 for both). Conclusions There was a significant relation between baseline PSA and incidence of AUR. However, there was no significant relationship between the serum PSA level and symptoms improvement in BPH.

Overall survival (OS) of African-American (AA) and Caucasian (CAU) men who received sipuleucel-T for metastatic castration-resistant prostate cancer (mCRPC): Final PROCEED analysis.

5035 Background: Prostate cancer risk and mortality are higher in AAs versus CAUs. Post-hoc analyses of pooled Phase 3 data (n = 737) suggested substantial OS benefit for AA men receiving sipuleucel-T (n = 33) vs placebo (n = 10) (McLeod 2012). Compared with pooled placebo patients (n = 249), number needed to treat for OS benefit at 3 years was 3 for AAs and 8 for all sipuleucel-T-treated patients (n = 488) (Moses 2019). Herein we analyzed PROCEED (NCT01306890), a large real-world registry, in which all patients received sipuleucel-T. Methods: In PROCEED, 1902 mCRPC patients received ≥1 sipuleucel-T infusion. OS of all AA (n = 221) and CAU (n = 1649) men were compared. Baseline prostate-specific antigen (PSA), the most important prognostic variable for OS after sipuleucel-T (Schellhammer 2013), substantially differed by race. Thus, OS for a PSA-matched cohort (n = 219 AA; n = 438 CAU) was compared and univariable/multivariable analyses were performed. Post-sipuleucel-T use of OS-prolonging anticancer interventions was also assessed. Results: After a median follow-up of 46.6 mo, median OS was 35.2 (all sipuleucel-T-treated AAs) and 29.9 mo (all sipuleucel-T-treated CAUs): HR 0.81, 95% CI 0.68–0.97; P = 0.03. In the PSA-matched cohort, median OS was 35.3 and 25.8 mo, respectively (HR 0.70, 95% CI 0.57–0.86; P < 0.001). Sipuleucel-T-treated AAs with lower baseline PSA had markedly longer median OS vs sipuleucel-T-treated CAUs. Among those with ≤ median baseline PSA (29.48 ng/ml), median OS was 54.3 mo (AA) vs. 33.4 (CAUs); HR 0.52, 95% CI 0.37–0.72; p < 0.001. Along with other known prognostic factors, AA race was independently associated with prolonged OS on detailed multivariable analyses (HR 0.60, 95% CI 0.48–0.74; p < 0.001) and confirmed on sensitivity analyses. Post-sipuleucel-T life-prolonging anti-cancer therapies were balanced between groups. Conclusions: Sipuleucel-T-treated AAs had significantly improved OS vs sipuleucel-T-treated CAUs. This analysis marks the largest known racial difference in OS in response to any therapy for mCRPC, a finding with implications for both prostate cancer pathophysiology and cancer immunotherapy. Clinical trial information: NCT01306890.