Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known. METHODS In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients. RESULTS A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88). CONCLUSIONS In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.

Background The ExoDx Prostate(IntelliScore) (EPI) test is a non-invasive risk assessment tool for detection of high-grade prostate cancer (HGPC) that informs whether to proceed with prostate biopsy. We sought to assess the impact of EPI on the decision to biopsy in a real-world clinical setting. Methods We conducted a prospective, randomized, blinded, two-armed clinical utility study that enrolled 1094 patients with 72 urologists from 24 urology practices. Patients were considered for prostate biopsy at enrollment based on standard clinical criteria. All patients had an EPI test; however, patients were randomized into EPI vs. control arms where only the EPI arm received results for their biopsy decision. Results In the EPI arm (N = 458), 93 patients received negative EPI scores of which 63% were recommended to defer biopsy by the urologist and 74% ultimately deferred. In contrast, 87% of patients with positive EPI scores were recommended to undergo biopsy with a 72% compliance rate to the urologist’s recommendation. This led to detection of 30% more HGPC compared to the control arm, and we estimate that 49% fewer HGPC were missed due to deferrals compared to standard of care (SOC). Overall, 68% of urologists reported that the EPI test influenced their biopsy decision. The primary reason not to comply with EPI results was rising PSA. Conclusion To our knowledge this is the first report on a PC biomarker utility study with a blinded control arm. The study demonstrates that the EPI test influences the overall decision to defer or proceed with a biopsy and improves patient stratification.

Toremifene decreased the incidence of prostate cancer by 1 year and had a tolerability profile comparable to that of placebo in a high risk population.

Purpose African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T. Patients and methods OS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan-Meier and Cox proportional hazard methodologies. Results Median follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68-0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57-0.86, P < 0.001) in the PSA-matched set. Median OS was longer in African Americans than in Caucasian men for both analysis sets, e.g., 35.3 and 25.8 months, respectively, in the PSA-matched set. Similar results were observed in the all patient set. Differences were larger when treatment began at lower baseline PSA; curves were more similar among patients with higher baseline PSA. In patients with baseline PSA below the median, the HR was 0.52 (95% CI: 0.37-0.72, P < 0.001), with median OS of 54.3 versus 33.4 months. Known prognostic factors and African American race (multivariable analyses; HR: 0.60, 95% CI: 0.48-0.74, P < 0.001) were independently associated with OS. Use of post-sipuleucel-T anticancer interventions was balanced between races. Conclusion In this exploratory analysis of a registry including nearly 12% African American men with mCRPC, OS was significantly different between African Americans and Caucasians, indicating further research is warranted.

BACKGROUND: PROCEED (), a large registry, evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). METHODS: PROCEED enrolled mCRPC patients receiving three biweekly sipuleucel-T infusions. Assessments included: overall survival (OS); serious adverse events (SAEs); cerebrovascular events (CVEs); and anticancer interventions (ACIs). Follow-up was ≥3 years, until death, or study withdrawal. RESULTS: 1976 patients (2011–2017) were followed for 46.6 months (median). Median age was 72 years and baseline median prostate-specific antigen was 15.0 ng/ml. 86.7% were Caucasians and 11.6% African American. 1902 patients had ≥1 sipuleucel-T infusion. Median OS was 30.7 (95% confidence interval [CI]: 28.6–32.2) months. Known prognostic factors were independently associated with OS on multivariable analysis. 1255 patients died, 964 (76.8%) from prostate cancer (PC) progression. Median time from first infusion to PC death was 42.7 (95% CI: 39.4–46.2) months. Incidence of sipuleucel-T-related SAEs was 3.9%. Incidence of CVEs was 2.8% and the rate per 100 person-years was 1.2 (95% CI: 0.9–1.6). CVE incidence among 11,972 mCRPC patients from the SEER-Medicare database was 2.8%; 1.5 [95% CI 1.4–1.7]/100 person-years. 77.7% of patients received ≥1 ACI (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium-223) after sipuleucel-T; 32.5% and 17.4% of patients experienced a 1- and 2-year treatment-free interval, respectively. CONCLUSIONS: PROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. Safety and tolerability of sipuleucel-T in PROCEED was consistent with previous findings.