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Background ENZA, a potent androgen receptor inhibitor, provides benefit in men with castration-resistant prostate cancer (CRPC). Objectives In post hoc analyses, the role of ENZA + ADT in mHSPC patients (pts) randomized within the multinational, double-blind, PBOcontrolled, Phase 3 ARCHES study (NCT02677896) was determined by disease volume and risk group stratification. Materials and methods mHSPC pts were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints included prostate-specific antigen (PSA) progression and radiographic responses, overall survival (OS), and quality of life (QoL). Analyses were completed by CHAARTED-defined disease volume and LATITUDE-defined risk groups. Results and conclusion 1150 pts were randomized (ENZA + ADT, n = 574; PBO + ADT, n = 576). Median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS (hazard ratio [95% CI] 0.39 [0.30, 0.50]; P < 0.0001). ENZA + ADT pts significantly benefited from prolonged rPFS in all subgroups (Table). Significant treatment benefits were observed with ENZA + ADT in several secondary clinical endpoints in the overall population and in both high and low disease volume and risk groups (Table). High QoL at baseline was maintained over time. OS data are immature. Adverse events (AEs) were reported in 85.1% of ENZA + ADT vs. 85.9% of PBO + ADT pts, with no unexpected AEs. ENZA + ADT treatment showed efficacy benefit across all mHSPC pts, irrespective of disease volume and risk group. Similar delays in rPFS, symptomatic skeletal events, PSA progression, castration resistance, and improvements in radiographic responses and PSA declines, with maintenance of high QoL over time, were observed. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Funding This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-develop

Background: In ARCHES (NCT02677896), ENZA + ADT reduced risk of radiographic progression and improved secondary outcomes in men with mHSPC over PBO + ADT. Here we report the final OS (after 356 events), a key secondary endpoint in ARCHES and a critical benchmark of clinical efficacy, which was immature at the time of primary analysis. Method(s): Men with de novo or relapsed mHSPC (n=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel use. At the time of data cut-off and unblinding, 180 (31.3%) patients treated with PBO + ADT crossed over to open-label ENZA + ADT. A stratified log-rank test was performed at a two-sided significance level of 0.04 for OS based on an O'Brien-Fleming boundary. Kaplan-Meier estimates of OS and time to subsequent antineoplastic therapy (TTNAnti) were reported and hazard ratios (HRs) were estimated from a stratified Cox proportional hazards model. Safety was assessed via treatment-emergent adverse events. Result(s): Baseline characteristics were similar between treatment arms. As of the data cut-off of May 28, 2021, 397 (34.5%) patients remained on treatment, with a median follow-up of 44.6 months). Median treatment duration was 40.2 months on ENZA + ADT, 13.8 months on PBO + ADT, and 23.9 months for crossover patients. ENZA + ADT extended survival vs PBO + ADT (HR 0.66; 95% confidence interval 0.53, 0.81; p<0.0001) [Table] with similar results in most prespecified subgroups. ENZA + ADT continued to prolong TTNAnti vs PBO + ADT. The safety profile of ENZA + ADT vs PBO + ADT was consistent with findings from the primary analysis. Conclusion(s): This final analysis demonstrates that ENZA + ADT significantly prolongs survival in men with mHSPC and, together with the acceptable safety profile, supports the clinical benefit of ENZA + ADT in men with mHSPC. [Formula presented] Clinical trial identification: NCT02677896. Editorial acknowledgement: This study was funded by Astellas Pha

Background: ENZA, a potent androgen receptor inhibitor, provides benefit in men with castration-resistant prostate cancer (CRPC). In post hoc analyses, the role of ENZA+ ADT inmHSPC patients (pts) randomized within the multinational, doubleblind, PBO-controlled, Phase 3 ARCHES study (NCT02677896) was determined by disease volume and risk group stratification. Method(s): mHSPC pts were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints included prostate-specific antigen (PSA) progression and radiographic responses, overall survival (OS), and quality of life (QoL). Analyses were completed by CHAARTED-defined disease volume and LATITUDE-defined risk groups. Result(s): 1150 pts were randomized (ENZA +ADT, n=574; PBO +ADT, n=576). Median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS (hazard ratio [95% CI] 0.39 [0.30, 0.50]; p<0.0001). ENZA+ ADT pts significantly benefited from prolonged rPFS in all subgroups (Table). Significant treatment benefits were observed with ENZA + ADT in several secondary clinical endpoints in the overall population and in both high and low disease volume and risk groups (Table). High QoL at baseline was maintained over time. OS data are immature. Adverse events (AEs) were reported in 85.1% of ENZA + ADT vs. 85.9% of PBO +ADT pts, with no unexpected AEs. Conclusion(s): ENZA+ ADT treatment showed efficacy benefit across all mHSPC pts, irrespective of disease volume and risk group. Similar delays in rPFS, symptomatic skeletal events, PSA progression, castration resistance, and improvements in radiographic responses and PSA declines, with maintenance of high QoL over time, were observed. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials.

Background: ENZA, a potent androgen receptor inhibitor, provides benefit in men with castration-resistant prostate cancer (CRPC). In post hoc analyses, the role of ENZA + ADT in mHSPC patients (pts) randomized within the multinational, double-blind, PBO-controlled, Phase 3 ARCHES study (NCT02677896) was determined by disease volume and risk group stratification. Method(s): mHSPC pts were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints included prostate-specific antigen (PSA) progression and radiographic responses, overall survival (OS), and quality of life (QoL). Analyses were completed by CHAARTED-defined disease volume and LATITUDE-defined risk groups. Result(s): 1150 pts were randomized (ENZA + ADT, n = 574; PBO + ADT, n = 576). Median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS (hazard ratio [95% CI] 0.39 [0.30, 0.50]; p < 0.0001). ENZA + ADT pts significantly benefited from prolonged rPFS in all subgroups (Table). Significant treatment benefits were observed with ENZA + ADT in several secondary clinical endpoints in the overall population and in both high and low disease volume and risk groups (Table). High QoL at baseline was maintained over time. OS data are immature. Adverse events (AEs) were reported in 85.1% of ENZA + ADT vs. 85.9% of PBO + ADT pts, with no unexpected AEs. [Table presented] Conclusion(s): ENZA + ADT treatment showed efficacy benefit across all mHSPC pts, irrespective of disease volume and risk group. Similar delays in rPFS, symptomatic skeletal events, PSA progression, castration resistance, and improvements in radiographic responses and PSA declines, with maintenance of high QoL over time, were observed. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Clinical trial identification: NCT02677896. Editorial acknowledgement: Beatrice Vetter-Ceriotti and Laure

Background: ENZA has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). ARCHES assessed the efficacy of ENZA with ADT in men with mHSPC, including pre-specified subgroups based on prior therapy. Method(s): ARCHES, a multinational, double-blind, Phase 3 study (NCT02677896), randomized patients (pts) with mHSPC 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel (doce) use. Primary endpoint was radiographic progression-free survival (rPFS; centrally assessed radiographic progression or death within 24 weeks of treatment discontinuation). Secondary endpoints included time to initiation of new antineoplastic therapy and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Result(s): 1150 men were randomized to ENZA (n = 574) or PBO (n = 576). Overall, 63% had high-volume disease, 18% had prior doce, and 91% had prior ADT or orchiectomy (orch). Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); significant improvements in rPFS were also reported in prior treatment subgroups. Secondary endpoints improved with ENZA + ADT (Table), with no significant impact in time to deterioration in urinary symptoms. OS data are immature. Grade 3-4 adverse events (AEs) were reported in 23.6% of ENZA pts vs. 24.7% of PBO pts with no unexpected AEs. Conclusion(s): ENZA + ADT significantly improved rPFS and other efficacy endpoints vs. PBO + ADT in men with mHSPC. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. (Table Presented).

The results of multicenter trial for efficacy of fluorescence diagnosis for bladder cancer with agent hexasens (SSC Scientific Research Institute Organic Intermediates and Dyes, Russia) based on hexyl ester of 5-aminolevulinic acid compared with routine cystoscopy are represented in the article. The study included 124 patients. All patients had intravesical instillation of 50 ml of 0,2% hexasens. The exposure time accounted for 1-2 h. After removal of the drug from bladder standard cystoscopy followed by fluorescence diagnosis was performed in every patient. During the local fluorescence spectroscopy the intravesical instillation of the agent hexasens was shown to induce selective accumulation of photoactive protoporphyrin IX in tumor cells comparing with intact bladder mucosa. During 1 h after intravesical instillation of hexasens solution the level of fluorescence of hexasens-induced protoporphyrin IX in the tumor was higher than that in surrounding intact mucosa at average in 5.8 fold. As compared with results of standard cystoscopy, fluorescence diagnosis improved the sensitivity of the method by 24.4% (from 75.6% to 100%), the accuracy - by 15.2% (from 83.3% to 98.5%) and negative predictive value - by 33.5% (from 66.5% to 100%). Fluorescence diagnosis gave an opportunity to detect additional tumor foci, which were invisible in white light, in 27.4% of patients. For fluorescence diagnosis in 4.0% of patients false-positive fluorescence of bladder mucosa was detected that was probably due to inflammation. None of patients received active dose of the drug hexasens had adverse reactions, changes in general well-being and blood and urine parameters. According to the results of the study fluorescence diagnosis with hexasens for bladder cancer is recommended for use in clinical practice.