Drug-drug interaction potential among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with novel androgen receptor inhibitors.

BACKGROUND: Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients are often older and use concurrent medications that increase the potential for drug-drug interactions (pDDIs). This study assessed pDDI prevalence in real-world nmCRPC patients treated with apalutamide, darolutamide, or enzalutamide. RESEARCH DESIGN AND METHODS: Castrated prostate cancer patients without metastases prior to androgen receptor inhibitor initiation were identified retrospectively via Optum Clinformatics Data Mart claims data (8/2019-3/2021). The top 100 concomitant medications were assessed for pDDIs. RESULTS: Among 1,515 patients (mean age: 77 ± 8 years; mean Charlson Comorbidity Index: 3 ± 3), 340 initiated apalutamide, 112 darolutamide, and 1,063 enzalutamide. Common concomitant medication classes were cardiovascular (80%) and central nervous system (52%). Two-thirds of the patients received ≥5 concomitant medications; 30 (30/100 medications) pDDIs were identified for apalutamide and enzalutamide each and 2 (2/100 medications) for darolutamide. Most pDDIs had risk ratings of C or D, but four for apalutamide were rated X. Approximately 58% of the patients on apalutamide, 5% on darolutamide, and 54% on enzalutamide had ≥1 identified pDDI. CONCLUSIONS: Results showed a higher frequency of pDDIs in patients receiving apalutamide and enzalutamide vs darolutamide. The impact of these could not be determined retrospectively. DDI risk should be carefully evaluated when discussing optimal therapy for patients with nmCRPC.

Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN.

BACKGROUND: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment. METHODS: Post-hoc analysis assessed patients receiving 240 mg/day apalutamide (525 TITAN and 806 SPARTAN) or placebo (527 TITAN and 401 SPARTAN) with ongoing ADT, stratified by age groups. Prostate-specific antigen declines, radiographic progression-free survival, metastasis-free survival, overall survival (OS), HRQoL and safety were assessed using descriptive statistics, Kaplan-Meier method, Cox proportional-hazards model and mixed-effects model for repeated measures. RESULTS: Hazard ratios (95% confidence intervals) generally favoured apalutamide plus ADT versus ADT alone across all endpoints regardless of age; e.g., OS values were 0.57 (0.40-0.80), 0.70 (0.54-0.91) and 0.74 (0.40-1.39) (TITAN) and 0.39 (0.19-0.78), 0.89 (0.69-1.16) and 0.81 (0.58-1.15) (SPARTAN) in patients aged <65, 65-79 and ≥80 years. Regardless of age, apalutamide also maintained HRQoL and was tolerated well with a potential trend in rates of adverse events increasing with age. Limitations include post-hoc nature and variability in sample size of age groups. CONCLUSIONS: Apalutamide plus ADT was an effective and well-tolerated option maintaining HRQoL in patients with mCSPC and nmCRPC regardless of age. CLINICAL TRIAL REGISTRATION: TITAN (NCT02489318); SPARTAN (NCT01946204).

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Early prostate-specific antigen response among Black and non-Black patients with advanced prostate cancer treated with apalutamide.

Aim: To assess reduction in prostate-specific antigen (PSA) levels among Black and non-Black patients treated with apalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC) or metastatic castration-sensitive prostate cancer (mCSPC). Patients & methods: Patients were identified from electronic medical data. PSA reduction (≥50%, ≥90% or below 0.2 ng/ml) after apalutamide initiation was assessed. Results: A total of 313 patients with nmCRPC and 260 patients with mCSPC were identified. The majority of patients treated with apalutamide achieved a 90% reduction in PSA regardless of indication or race. The proportion of patients achieving a PSA reduction at any level was similar among Black and non-Black patients and was consistent with apalutamide phase III trials. Conclusion: In routine clinical practice, apalutamide consistently produced reduction in PSA levels in Black and non-Black men with nmCRPC or mCSPC.

Low Body Weight as a Risk Factor for Apalutamide-related Cutaneous Adverse Events.

BACKGROUND/AIM: Therapeutic strategies for prostate cancer are currently undergoing a paradigm shift due to the advent of next-generation androgen receptor inhibitors. Among these inhibitors, apalutamide is regarded as a key drug because of its effectiveness. However, risk factors for and the timing of the onset of apalutamide-related cutaneous adverse events remain unclear. Therefore, the present study investigated key risk factors for and timing of the onset of apalutamide-related cutaneous adverse events. PATIENTS AND METHODS: Sixty-two Japanese patients with non-metastatic castration-resistant prostate cancer treated with 240 mg/day of apalutamide were enrolled in the present study. RESULTS: Twenty-four patients (38.7%) developed cutaneous adverse events. Multivariable logistic regression analysis of age, height, and body weight identified body weight as a significant predictive factor for the incidence of cutaneous adverse events (p=0.019). When the mean body weight of patients (63.80 kg) was set as the cut-off value, the Kaplan-Meier analysis revealed that the risk of cutaneous adverse events was significantly increased in those with a body weight <63.8 kg (p=0.003, the log-rank test). The analysis also showed that cutaneous adverse events developed within the first 6 months regardless of body weight. CONCLUSION: A lower body weight is a significant risk factor for apalutamide-related cutaneous adverse events and their onset is within 6 months of initiation of therapy.

Real-world burden of adverse events for apalutamide- or enzalutamide-treated non-metastatic castration-resistant prostate cancer patients in the United States.

BACKGROUND: Second-generation androgen receptor inhibitors (ARIs) have been associated with adverse events (AEs) such as fatigue, falls, fractures, and rash in non-metastatic castration-resistant prostate cancer (nmCRPC) patients as identified in clinical trials. The objectives of this study were to describe the incidence and management of AEs in patients receiving apalutamide and enzalutamide. METHODS: This retrospective chart review study was conducted in nmCRPC-treating sites in the United States. Patients starting apalutamide or enzalutamide between February 1, 2018 and December 31, 2018 were included and any AEs they experienced were recorded. AEs, including those considered to be of special interest as defined in the pivotal clinical trials of the second-generation ARIs, were analyzed and grouped retrospectively in this study. Detailed chart data (patient demographics, clinical characteristics, treatment history, type of AE, outcomes, and resource utilization) were then collected for a randomly selected subset among patients with ≥1 AE to characterize AEs and their management. Descriptive results were summarized. RESULTS: Forty-three sites participated in the study. A total of 699 patients were included, of whom 525 (75.1%) experienced ≥1 AE. The most common AEs were fatigue/asthenia (34.3%), hot flush (13.9%), and arthralgia (13.6%). In the subset of 250 patients randomly selected from those who experienced ≥1 AE, patients were primarily White (72.0%), the mean age was 71 years, 86.0% had an Eastern Cooperative Oncology Group score of 0-1 at nmCRPC diagnosis, and the average prostate specific antigen (PSA) value at diagnosis was 23.2 ng/mL. PSA-doubling time < 10 months was chosen as reason to initiate treatment in 40% of patients. The median duration of follow-up was 1.1 years, with 14.4% of patients progressing to metastasis by end of study period. Grade 3-4 and Grade 5 AEs occurred in 14.4 and 0.4% of patients, respectively. Actions taken to manage AEs included AE-directed treatment (38.0%), ARI discontinuation (10.4%), dose reduction (7.6%), and AE-related hospitalization (4.8%). CONCLUSIONS: This study highlights the burden of AEs among nmCRPC patients treated with apalutamide or enzalutamide, providing a relevant real-world benchmark as clinical trial evidence and the treatment landcape for nmCRPC continues to evolve.

Dermatological Adverse Events in Prostate Cancer Patients Treated with the Androgen Receptor Inhibitor Apalutamide.

PURPOSE: Patients with prostate cancer (PCa) treated with apalutamide frequently develop rash. We aim to characterize apalutamide-related dermatological adverse events (dAEs) and management. MATERIALS AND METHODS: We assessed 303 patients with PCa treated with apalutamide. DAE frequency and time to onset were calculated and clinicopathological features and management described. Associations between dAE occurrence and clinical trial participation, as well as abiraterone/prednisone exposure were detected using logistic regression models. RESULTS: Seventy-one (23.4%) patients had all-grade dAE occurring at a median of 77 (IQR: 30-135) days post-exposure. Twenty (6.6%) dAE-related therapy interruptions included: 8 (2.6%) with dose maintained on rechallenge, 7 (2.3%) with dose reduction and 5 (1.7%) with discontinuation. Common dAEs were maculopapular rashes (33.8%) and xerosis (32.4%). Seven (77.8%) of 9 histological analyses of skin biopsies supported a drug reaction. No significant differences in laboratory hematological, hepatic and renal function were detected between dAE and no dAE cohorts. Most treated grade 1/2 dAEs (29, 40.8%) required topical steroids (14, 19.7%); few required oral steroids (3, 4.2%) ± oral antihistamines. Most grade 3 dAEs (8, 11.3%) required oral/topical steroids (5, 7.0%); few required topical steroids (3, 4.2%) ± oral antihistamines. Clinical trial patients (180, 59.4%) were more likely to report dAEs than those in the off-trial setting (OR=5.1 [95% CI 2.55-10.12]; p <0.001). Of clinical trial patients, concomitant abiraterone/prednisone recipients (109 of 180, 60.6%) were more likely to report dAEs (OR=3.1 [95% CI 1.53-6.17]; p=0.002). CONCLUSIONS: Apalutamide-related dAEs are frequent and can be managed with topical ± oral steroids. With expanded approval of apalutamide, dAE identification and management are essential.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial.

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Apalutamide-induced severe interstitial lung disease: A report of two cases from Japan.

Apalutamide, a competitive inhibitor of the androgen receptor, is being increasingly used for the treatment of prostate cancer. There have been few reports of interstitial lung disease in clinical trials of apalutamide. However, two cases of apalutamide-induced interstitial lung disease with respiratory failure in Japanese males, who were successfully treated with high-dose corticosteroids, are presented here. These cases suggest that clinicians should be alert to the potentially life-threatening risk of pulmonary toxicity associated with apalutamide treatment.

Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study.

PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed. RESULTS: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports. CONCLUSION: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer.

PURPOSE: No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons. MATERIALS AND METHODS: Individual patient data from the phase III ARAMIS trial (NPLACEBO=553; NDAROLUTAMIDE=943) were selected and reweighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (NPLACEBO=401; NAPALUTAMIDE=806) and PROSPER (NPLACEBO=468; NENZALUTAMIDE=933) trials. Only baseline factors consistently reported across trials were included as matching covariates. Both indirect comparisons matched on age, prostate specific antigen level and doubling time, Eastern Cooperative Oncology Group performance status, Gleason score, and bone-sparing agent use. Darolutamide vs apalutamide also matched on prior surgery and darolutamide vs enzalutamide also matched on region. Risk differences and odds ratios were calculated for adverse events and hazard ratios for metastasis-free survival. RESULTS: No differences in metastasis-free survival hazard ratios were found after matching in either comparison. However, fall, fracture and rash rates were statistically significantly lower in favor of darolutamide vs apalutamide. Fall, dizziness, mental impairment, fatigue and severe fatigue rates were statistically significantly lower in favor of darolutamide vs enzalutamide. CONCLUSIONS: While metastasis-free survival did not differ across drugs in these cross-trial indirect comparisons, darolutamide showed a favorable safety and tolerability profile in prespecified adverse events vs apalutamide and enzalutamide. Consideration of these adverse events is important in clinical decision-making and treatment selection in nonmetastatic castration-resistant prostate cancer.

Darolutamide in hormone-sensitive and castration-resistant prostate cancer.

Introduction: Important changes in the treatment of prostate cancer have taken place in recent years. Non-metastatic castration-resistant prostate cancer (nmCRPC) has been clinically delineated. In this setting, three drugs have been approved in high-risk disease: apalutamide, enzalutamide and darolutamide.Areas covered:This manuscript aims to profile darolutamide, its clinical development, pharmacologic properties, efficacy and safety. We presented the results of published clinical studies, but we also investigated ongoing ones.Expert opinion: An indirect comparison with the other two aforementioned drugs emerged. While the clinical efficacy is comparable, the toxicity profile is different for darolutamide, resulting in greater tolerance. We must wait for the results of the trials that study darolutamide in hormone-sensitive disease, both in the metastatic phase and in the localized phase. Clinical experience will also be important to determine ever more personalized treatments for patients.

Apalutamide, darolutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer: a meta-analysis.

Aim: Comparison of the efficacy/safety/health-related quality of life of apalutamide, enzalutamide and darolutamide in Phase III clinical trials involving patients with nonmetastatic castration-resistant prostate cancer was performed. Materials & methods: Relevant studies were identified by searching PubMed as well as conference abstracts reporting updated overall survival. Three pivotal trials were identified, SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), and form the basis of this analysis. Results: All three drugs significantly prolonged metastasis-free survival, prostate-specific antigen response and overall survival versus placebo, and were generally well tolerated. Conclusion: Drug selection will likely be influenced by tolerability/safety and other factors, such as the propensity for drug-drug interactions and the presence of comorbidities, that affect the risk-benefit balance in individual patients.

Apalutamide for the treatment of metastatic castration-sensitive prostate cancer.

Prostate cancer is the fifth leading cause of cancer-related death among men with the majority of deaths linked to metastatic disease. Accumulating clinical data have confirmed the substantial survival benefit of the addition of docetaxel or androgen signaling inhibitors to androgen deprivation therapy for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). Apalutamide, a next-generation androgen receptor inhibitor, has recently been shown to provide an added survival benefit in the treatment of mCSPC and consequently approved for this indication. This review summarizes the body of evidence with regards to the preclinical activity and clinical efficacy of apalutamide with a specific focus on its efficacy in the treatment of mCSPC.

Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study.

BACKGROUND: A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). METHODS: This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN ( NCT01946204 ; patients with non-metastatic castration-resistant PC [nmCRPC]) and TITAN ( NCT02489318 ; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 ( NCT02162836 ; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. RESULTS: Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 h) (AUC0-24, ss) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. CONCLUSIONS: No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment. TRIAL REGISTRATION: Retrospective pooled analysis of NCT01946204 , NCT02489318 , and NCT02162836 .

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer.

Apalutamide (Erleada®) is an oral selective androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. It is approved in the EU and the USA for the treatment of adult men with metastatic castration-sensitive prostate cancer (mCSPC). In a multinational, phase III study (TITAN) in this patient population, the addition of apalutamide (240 mg once daily) to androgen deprivation therapy (ADT) significantly improved median radiographic progression-free survival (rPFS), median overall survival (OS) and the median time to cytotoxic chemotherapy, while maintaining health-related quality of life (HR-QOL) and not substantially differing from placebo plus ADT in safety. Although mature OS data are awaited with interest, the addition of apalutamide to ADT extends the treatment options available for standard of care in adult men with mCSPC.