BACKGROUND: This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan.
METHODS: The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS.
RESULTS: The median observation period was 46.4 months, and the median age of patients at diagnosis was 71 years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29 months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2 ng/mL in a median time of 4.7 months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9 months.
CONCLUSIONS: These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.

UNASSIGNED: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC.
UNASSIGNED: We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis.
UNASSIGNED: In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications.
UNASSIGNED: Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

OBJECTIVE: Addition of darolutamide to androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (OS) in ARASENS (NCT02799602). Here we report on prostate-specific antigen (PSA) responses and their association with outcomes.
METHODS: ARASENS is an international, double-blind, phase 3 study in patients with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to darolutamide 600 mg orally twice daily (n = 651) or placebo (n = 654), both with ADT + docetaxel. The proportion of patients with undetectable PSA (<0.2 ng/ml) and time to PSA progression (≥25% relative and ≥2 ng/ml absolute increase from nadir) were compared between groups in prespecified exploratory analyses. PSA outcomes by disease volume and the association of undetectable PSA with OS and times to castration-resistant prostate cancer (CRPC) and PSA progression were assessed in post hoc analyses.
UNASSIGNED: The proportion of patients with undetectable PSA at any time was more than doubled with darolutamide versus placebo, at 67% versus 29% in the overall population, 62% versus 26% in the high-volume subgroup, and 84% versus 38% in the low-volume subgroup. Darolutamide delayed time to PSA progression versus placebo, with hazard ratios of 0.26 (95% confidence interval [CI] 0.21-0.31) in the overall population, 0.30 (95% CI 0.24-0.37) in the high-volume subgroup, and 0.093 (95% CI 0.047-0.18) in the low-volume subgroup. Undetectable PSA at 24 wk was associated with longer OS, with a hazard ratio of 0.49 (95% CI 0.37-0.65) in the darolutamide group, as well as longer times to CRPC and PSA progression, with similar findings in the disease volume subgroups.
CONCLUSIONS: Darolutamide + ADT + docetaxel led to deep and durable PSA responses in patients with high- or low-volume mHSPC. Achievement of undetectable PSA (<0.2 ng/ml) was correlated with better clinical outcomes.
RESULTS: For patients with metastatic hormone-sensitive prostate cancer being treated with androgen deprivation therapy and docetaxel, PSA (prostate-specific antigen) became undetectable (below 0.2 ng/ml) in 67% of those also receiving darolutamide versus 29% of patients also receiving placebo. On average, patients achieving undetectable PSA lived longer than patients with detectable PSA.

UNASSIGNED: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy.
UNASSIGNED: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide.
UNASSIGNED: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating.
UNASSIGNED: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing.
UNASSIGNED: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study\'s hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.

UNASSIGNED: This study assessed the treatment patterns, healthcare resource utilization (HRU), costs, and annual prevalence and incidence of metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) in China.
UNASSIGNED: A retrospective study was conducted using electronic medical records (EMR) of patients with prostate cancer from three tertiary-care hospitals in China between January 2014 and March 2021. Descriptive statistics were used to analyze study outcomes.
UNASSIGNED: In total, 1086 patients with mHSPC and 679 patients with nmCRPC were included. From 2015 to 2020, the annual percentage of prevalent and incident cases of mHSPC decreased from 22.4% to 20.0% and 11.1% to 6.9%, respectively; for nmCRPC, these increased from 3.8% to 13.6% and 3.3% to 8.4%. Androgen-deprivation therapy and first-generation antiandrogens (bicalutamide or flutamide) were the most frequently prescribed prostate cancer-related medications at baseline and follow-up in patients with mHSPC. Bicalutamide was the most frequently prescribed prostate cancer-related medication during follow-up in patients with nmCRPC. For mHSPC, inpatient admission costs were the highest, with the median (interquartile range) costs per person-month being USD 403.00 (USD 85.50-1226.20), whereas outpatient visit costs were the highest for nmCRPC (USD 372.60 [USD 139.50-818.50]).
UNASSIGNED: EMR-based study design did not capture treatment patterns, HRU and associated costs, and healthcare encounters that occurred outside of participating hospitals, which could have led to underestimation of the true disease burden.
UNASSIGNED: A contrasting trend of a decline in the prevalence and incidence of mHSPC and an increase in these for nmCRPC was observed between 2015 and 2020 in China. Androgen-deprivation therapy and first-generation antiandrogens were the most frequently prescribed prostate cancer-related medications. Healthcare resource utilization was driven by inpatient costs in mHSPC and outpatient costs in nmCRPC.

To evaluate the efficacy and safety of apalutamide prostate cancer compared to the pivotal trials patients and to identify the first subsequent therapy in a real-world setting.
The study is prospective and observational based on real-world evidence, performed by different medical disciplines and eight academics centres around Barcelona, Spain. It included all patients with metastatic hormone-sensitive prostate cancer (mHSPC) and high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide from June 2018 to December 2022.
Of 227 patients treated with apalutamide, 10% had ECOG-PS 2, and 41% were diagnosed with new-generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. Treatment-related adverse events occurred in 40.1% of mHSPC and 44.4% of nmCRPC. After discontinuation of apalutamide due to disease progression, 54.5% in mHSPC and 75% in nmCRPC started chemotherapy, while after discontinuation because of adverse events, 73.3% in mHSPC and 100% in nmCRPC continued with other hormonal-therapies.
The efficacy and safety of apalutamide were similar to that described in the pivotal trials, despite including an older and more comorbid population. Usually, subsequent therapies after apalutamide differed depending on the reason for discontinuation: by disease progression started chemotherapy and by adverse events hormonal sequencing.

UNASSIGNED: The role of prednisone in the prevention of androgen receptor antagonist-related rash and treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. This pilot trial (ChiCTR2200060388) aimed to investigate the feasibility of apalutamide combined with androgen deprivation therapy (ADT) and short-course low-dose prednisone in the treatment of mHSPC.
UNASSIGNED: All patients received apalutamide and ADT and were randomly divided into two groups based on the administration of oral prednisone or not (control group). The primary endpoint was the incidence of rash. The secondary endpoint included the proportions of patients with a decline in PSA ≥50% from baseline, PSA ≥90% from baseline, and decreased to PSA ≤0.2 ng/mL.
UNASSIGNED: Between June 2021 and March 2022, a total of 83 patients were enrolled (41 in the prednisone group and 42 in the control group). During the 6-month follow-up, the incidence of rash was significantly lower in the prednisone group compared with the control group (17.1% vs. 38.1%, P=0.049). There were no significant differences in the incidence of other adverse events, the number of patients who required dose adjustment (reduction, interruption, or discontinuation) of apalutamide due to rash, the number of patients with prostate-specific antigen (PSA) decreased by ≥50%, the number of patients with PSA decrease ≥90%, and the number of patients with PSA ≤0.2 ng/mL between the two groups. All patients with diabetes had stable glycemic control with no glucose-related adverse events.
UNASSIGNED: In patients with mHSPC, the addition of short-course low-dose prednisolone to apalutamide plus ADT can reduce the incidence of rash without risk of other adverse events.

BACKGROUND: In the ARASENS trial (NCT02799602), darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR, 0.68; 95% CI, 0.57-0.80; P < .0001) compared with placebo plus ADT with docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We present efficacy and safety of darolutamide versus placebo in Black patients from ARASENS.
METHODS: Patients with mHSPC were randomized 1:1 to darolutamide 600 mg or placebo twice daily in combination with ADT and docetaxel. The primary endpoint was overall survival. Key secondary endpoints included time to castration-resistant prostate cancer (CRPC) and safety.
RESULTS: In ARASENS, 54 Black patients received darolutamide (n = 26) or placebo (n = 28) plus ADT and docetaxel. In Black patients, overall survival favored darolutamide versus placebo (median, not reached vs. 38.7 months; stratified HR, 0.41; 95% CI, 0.17-1.02), with 4-year survival rates of 62% versus 41%. The darolutamide group also had longer time to CRPC compared with the placebo group (median, not reached vs .12.6 months; HR, 0.09; 95% CI, 0.02-0.30). The safety profile of darolutamide in Black patients was consistent with that observed for the overall ARASENS population (grade 3/4 treatment-emergent adverse events, TEAEs: 61.5% vs. 66.1%; serious TEAEs: 42.3% vs. 44.8%).
CONCLUSIONS: In this small population of Black patients with mHSPC from the ARASENS trial, darolutamide was associated with an improvement in survival and time to CRPC and was well tolerated. Efficacy and safety findings in Black patients were consistent with the overall ARASENS population.

Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal.
TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS).
From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) (P = .001), opioid use (P = .004), bone metastases number (P < .001), baseline PSA (P = .006), Hb (P < .001), ALP (P < .001) and LDH (P = .002), time between ADT and docetaxel start (P = .018), 3-month PSA (P < .001) and ALP (P < .001), and number of docetaxel cycles (P < .001). OS-related variables were PSA at diagnosis (P = .024), primary tumor treatment (P = .022), baseline pain (P = .015), opioid use (P < .001), bone metastases number (P < . 001), baseline Hb (P < .001), ALP (P < .001) and LDH (P = .001), NLR ratio (P = .039), 3-month PSA (P < .001) and ALP (P < .001) and docetaxel cycles number (P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS.
Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy.

Over the past decade, the treatment of metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly. Current guidelines suggest the use of androgen deprivation therapy (ADT) plus an additional systemic therapy, regardless of disease burden and risk, based on phase 1 evidence showing improved overall survival. We sought to describe treatment patterns of patients with mCSPC in the province of Alberta.
This was a retrospective, population-based, cohort study of male patients aged ≥18 with mCSPC at the time of diagnosis and who initiated ADT between 1 January 2016 and 31 December 2020. Data were obtained from the Alberta Cancer Registry. Patients were assigned to an ADT-alone cohort or a treatment intensification cohort (cohorts 2-5). The primary objectives of this study were to describe baseline characteristics and the treatment of mCSPC patients who initiated ADT with or without treatment intensification. Overall survival between cohorts was a secondary objective. Descriptive statistics were used to describe differences in baseline characteristics of each cohort. Overall survival was calculated using the Kaplan-Meier method. All statistical tests were two-sided and are used to call out likely cohort differences descriptively.
Between 1 January 2016 and 31 December 2020, we identified a total of 960 patients with mCSPC (median age 74 years, IQR 66-82). Most patients received ADT alone (67%), followed by ADT plus abiraterone (18%), ADT plus docetaxel (12%), and ADT plus enzalutamide or apalutamide (3%). Over the study period, we observed an increase in the utilization of treatment intensification over time, in particular, the increased use of androgen-receptor-axis-targeted (ARAT) therapies. Patients who received ADT alone were older, were more likely to have more than one comorbid condition, had fewer sites of metastatic disease, and were less likely to be on opioid medications.
In this study, we show that patients who received ADT alone as treatment for mCSPC are older, have more comorbidities, and have less extensive disease. While there has been a decline over time in the number of patients treated with ADT alone, over 50% of all patients with mCSPC continue to receive ADT alone. Further work is needed to understand barriers to treatment intensification and for knowledge translation initiatives to improve the treatment of patients with mCSPC.