Safety Of Apalutamide Research Articles

Real-World Clinical Outcomes and Treatment Patterns Among Black and Non-Black Patients With Prostate Cancer Initiated on Apalutamide in a Urology Setting

Background: The use of androgen receptor signaling inhibitors, including apalutamide, in combination with androgen deprivation therapy is recommended for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC). Objective: To describe real-world treatment patterns and clinical outcomes among patients with mCSPC or nmCRPC who initiated apalutamide in the United States. Methods: A retrospective cohort study of patients with mCSPC or nmCRPC who initiated apalutamide was conducted using electronic medical record data from US community-based urology practices (Feb. 1, 2017–April 1, 2022). Persistence with apalutamide was reported at 6-, 12-, and 18-months post treatment initiation. Clinical outcomes described up to 24 months after apalutamide initiation using Kaplan-Meier analyses included progression to castration resistance, castration resistance-free survival (CRFS), and metastasis-free survival (MFS). Outcomes were reported separately based on mCSPC or nmCRPC status and race (ie, Black or non-Black). Results: This study included 589 patients with mCSPC (mean age, 75.9 years) and 406 patients with nmCRPC (mean age, 78.8 years). Using a treatment gap of >90 days, persistence with apalutamide at 12 months remained high for both the mCSPC (94.9%) and nmCRPC (92.7%) cohorts, and results were descriptively similar among Black and non-Black patients, and when a treatment gap of >60 days was considered. In patients with mCSPC, overall progression to castration resistance rates at 12 and 24 months were 20.9% and 33.5%, and overall CRFS rates were 76.2% and 62.0%, respectively. In patients with nmCRPC, overall MFS rates at 12 and 24 months were 89.7% and 75.4%, respectively. Rates of these clinical outcomes were descriptively similar between Black and non-Black patients. Discussion: While clinical trials have demonstrated the efficacy and safety of apalutamide, there is limited real-world data describing treatment persistence and clinical outcomes among patients with mCSPC and nmCRPC who initiated apalutamide. Conclusions: In this real-world study of patients with mCSPC or nmCRPC initiated on apalutamide, treatment persistence was high and apalutamide demonstrated robust real-world effectiveness with respect to progression to castration resistance, CRFS, and MFS, overall and among Black and non-Black patients.

Real-World Clinical Outcomes and Treatment Patterns Among Black and Non-Black Patients With Prostate Cancer Initiated on Apalutamide in a Urology Setting.

Background: The use of androgen receptor signaling inhibitors, including apalutamide, in combination with androgen deprivation therapy is recommended for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC). Objective: To describe real-world treatment patterns and clinical outcomes among patients with mCSPC or nmCRPC who initiated apalutamide in the United States. Methods: A retrospective cohort study of patients with mCSPC or nmCRPC who initiated apalutamide was conducted using electronic medical record data from US community-based urology practices (Feb.1, 2017-April 1, 2022). Persistence with apalutamide was reported at 6-, 12-, and 18-months post treatment initiation. Clinical outcomes described up to 24 months after apalutamide initiation using Kaplan-Meier analyses included progression to castration resistance, castration resistance-free survival (CRFS), and metastasis-free survival (MFS). Outcomes were reported separately based on mCSPC or nmCRPC status and race (ie, Black or non-Black). Results: This study included 589 patients with mCSPC (mean age, 75.9 years) and 406 patients with nmCRPC (mean age, 78.8 years). Using a treatment gap of >90 days, persistence with apalutamide at 12 months remained high for both the mCSPC (94.9%) and nmCRPC (92.7%) cohorts, and results were descriptively similar among Black and non-Black patients, and when a treatment gap of >60 days was considered. In patients with mCSPC, overall progression to castration resistance rates at 12 and 24 months were 20.9% and 33.5%, and overall CRFS rates were 76.2% and 62.0%, respectively. In patients with nmCRPC, overall MFS rates at 12 and 24 months were 89.7% and 75.4%, respectively. Rates of these clinical outcomes were descriptively similar between Black and non-Black patients. Discussion: While clinical trials have demonstrated the efficacy and safety of apalutamide, there is limited real-world data describing treatment persistence and clinical outcomes among patients with mCSPC and nmCRPC who initiated apalutamide. Conclusions: In this real-world study of patients with mCSPC or nmCRPC initiated on apalutamide, treatment persistence was high and apalutamide demonstrated robust real-world effectiveness with respect to progression to castration resistance, CRFS, and MFS, overall and among Black and non-Black patients.

Apalutamide and Goserelin for Androgen Receptor-Positive Salivary Gland Carcinoma: A Phase II Nonrandomized Clinical Trial, YATAGARASU.

To assess the efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive unresectable or recurrent/metastatic salivary gland carcinoma. This trial was an open-label, single-arm, multicenter phase II study. Patients with histologically confirmed unresectable or recurrent/metastatic salivary gland carcinoma with AR expression were included. The primary endpoint was the overall response rate (ORR) according to RECIST v1.1 by an independent central radiology review in the first 24 response-evaluable (RE) patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded. A total of 31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by independent central radiology review was 25.0% [6/24 patients; 95% confidence interval, 9.8%-46.7%; P = 0.11 (one-sided)], which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR positivity ≥70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain. Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive salivary gland carcinoma and safety consistent with prior experience in prostate cancer.

Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg (n = 111) or placebo (n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

Efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer (GENESIS): protocol for a multicentre, open-label, single-arm clinical trial

IntroductionThis is a multicentre, open-label, single-arm clinical trial to evaluate the efficacy and safety of apalutamide in patients with metastatic castration-resistant prostate cancer.Methods and analysisThe trial will be performed at...

The effect of prior docetaxel (DOC) treatment on efficacy and safety of apalutamide (APA) plus androgen deprivation therapy (ADT) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) from TITAN.

89 Background: Addition of androgen receptor signaling inhibitors to ADT + DOC has been shown to improve clinical outcomes in pts with mCSPC. TITAN, a placebo-controlled phase 3 study, showed that APA + ADT improved overall survival (OS) and other clinical outcomes in mCSPC (Chi, J Clin Oncol 2021). This post hoc analysis of TITAN evaluated outcomes in pts who had received DOC prior to treatment with APA + ADT versus those who did not. Methods: In TITAN, 1052 pts were randomized 1:1 to APA (240 mg QD) or placebo added to ongoing ADT. We assessed radiographic progression-free survival (rPFS), OS, and time to prostate-specific antigen (PSA) progression in pts receiving DOC and ADT prior to adding APA vs those receiving only ADT plus APA. Outcomes by prior DOC were also assessed in pts with high- or low-volume disease at randomization (baseline [BL]) per adapted CHAARTED criteria, or those with matched BL characteristics. A Cox proportional hazards model was used to derive hazard ratios (HRs) and p values. rPFS was assessed using the first interim analysis cutoff (23 mo median follow-up); OS and time to PSA progression were assessed using the final analysis cutoff (44 mo median follow-up). Results: A total of 58/525 (11%) pts from the APA + ADT group had received DOC prior to randomization: 76% (n = 44) had high-volume disease, 62% (n = 36) had bone-only metastases, 16% (n = 9) had visceral metastases, and 59% (n = 34) had > 10 bone lesions. In the overall APA-treated population and in the subset of pts with high-volume disease, OS, rPFS, and time to PSA progression were similar in those who received prior DOC and those who did not (Table). Pts with low-volume disease also had similar results, although the number of pts was small. Clinical outcomes in pts with matched BL characteristics (including PSA and time from initial diagnosis to randomization, among others) were similar regardless of prior use of DOC (Table). The safety profile of APA was not substantially different between pts with or without prior DOC. Limitations of this analysis include lack of data on tumor volume and other disease characteristics at the initiation of prior DOC treatment; interpretation was based on small number of pts with prior DOC (only 11% of TITAN pts), most notably in the rPFS analysis. Conclusions: Prior use of DOC in pts with mCSPC did not further improve clinical benefits of APA + ADT in TITAN. Clinical trial information: NCT02489318. [Table: see text]

618P Apalutamide (APA) for advanced prostate cancer in older patients (pts): Combined analysis of TITAN & SPARTAN

In TITAN and SPARTAN, APA added to continuous androgen deprivation therapy (ADT) improved prostate-specific antigen (PSA) response, radiographic progression-free survival (rPFS), metastasis-free survival (MFS), and overall survival (OS) in pts with metastatic castration-sensitive prostate cancer (mCSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). We assessed efficacy and safety of APA in age groups from both studies.

Apalutamide for metastatic, castration-sensitive prostate cancer in the Japanese population: A subgroup analysis of the randomized, double-blind, placebo-controlled phase 3 TITAN study.

To evaluate the efficacy and safety of apalutamide+androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration-sensitive prostate cancer from the phase 3, randomized, global TITAN study. Men with metastatic castration-sensitive prostate cancer randomly (1:1) received 240mg apalutamide+androgen deprivation therapy or matching placebo+androgen deprivation therapy. The primary efficacy endpoints were radiographic progression-free survival and overall survival. Secondary efficacy endpoints were time to cytotoxic chemotherapy, pain progression, chronic opioid use, and skeletal-related events. Safety was also assessed. Of the 1052 patients included in the TITAN study, 51 (4.85%) were Japanese (apalutamide group, n=28; placebo group, n=23). In all, 81.8% of patients in the apalutamide and 71.8% in the placebo group did not experience radiographic progression or death, and the hazard ratio for radiographic progression-free survival favored treatment with apalutamide (hazard ratio 0.712, 95% confidence interval 0.205-2.466; P=0.59). At 24months, 85.7% of patients in the apalutamide group and 81.5% in the placebo group were alive, and the hazard ratio for overall survival favored apalutamide (hazard ratio 0.840, 95% confidence interval 0.210-3.361; P=0.805). In the interim analysis, the median radiographic progression-free survival and overall survival were not reached in the apalutamide group and time to cytotoxic chemotherapy was delayed following apalutamide treatment. The safety profile of apalutamide in the Japanese subpopulation was comparable with that of the global population, except for skin rash. The results of the present analyses suggest that apalutamide+androgen deprivation therapy in Japanese patients had favorable efficacy compared with androgen deprivation therapy alone, and these findings are comparable to those in the overall population. Apalutamide+androgen deprivation therapy can be considered as one of the therapeutic options for a broad spectrum of metastatic castration-sensitive prostate cancer regardless of prior treatment and disease extent in Japanese patients.

Efficacy and safety of apalutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase-3 study

BackgroundIn the global Phase-3 Selective Prostate Androgen Receptor Targeting with ARN-509 study, apalutamide plus ongoing androgen deprivation therapy (ADT) significantly increased metastasis-free survival (MFS) and improved other clinical outcomes in men with nonmetastatic castration-resistant prostate cancer (nm-CRPC) who were at high risk of developing metastases. In this subpopulation analysis of Selective Prostate Androgen Receptor Targeting with ARN-509 study, the efficacy and safety of apalutamide plus ADT were evaluated in Japanese patients with nm-CRPC.MethodsThe primary efficacy end point was MFS. Secondary efficacy end points were time to metastasis, progression-free survival, symptomatic progression, initiation of cytotoxic chemotherapy, and overall survival. Safety and pharmacokinetic parameters were also assessed.ResultsFifty-five Japanese patients with ongoing ADT were randomized (apalutamide: n = 34, placebo: n = 21). Median treatment duration was 5.7 months in the apalutamide group and 11.0 months in the placebo group. Median MFS was not reached in the apalutamide group (95% confidence interval: 10.97, not estimable) and was 18.23 months (95% confidence interval: 11.04, 18.50) in the placebo group. Secondary end points were improved in the apalutamide group. The safety profile of apalutamide with ADT was comparable with the global population, and no new safety signals were identified in this Japanese subpopulation. Although, apalutamide exposure tended to be higher in the Japanese subpopulation compared with the non-Japanese population, this was likely to be explained by body weight and considered not clinically meaningful.ConclusionIn the Japanese subpopulation, treatment with apalutamide with ADT resulted in favorable efficacy outcomes with comparable benefit-risk profile to the global population with nm-CRPC who are at high-risk of developing metastases.

Age-related efficacy and safety of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in subgroups of patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Post hoc analysis of SPARTAN.

5024 Background: SPARTAN, a randomized phase 3 placebo (PBO)-controlled study in pts with high-risk nmCRPC and PSA doubling time ≤ 10 mo, showed that, compared with PBO, addition of APA to ongoing ADT treatment (tx) prolonged metastasis-free survival (MFS) by > 2 y, reduced the risk of symptomatic progression by 55%, and increased second progression-free survival (PFS2), which is the time from randomization to disease progression on first subsequent anticancer tx, or death. The impact of APA in terms of benefit and safety profile was evaluated in pts aged < 65, 65-74, and ≥ 75 y. Methods: Pts with nmCRPC were randomized 2:1 to APA (240 mg QD) or PBO; ADT was continuous. APA effect was analyzed by Cox models and Kaplan-Meier methods across age subgroups. Results: Baseline characteristics among age groups were similar, although ECOG PS 1 vs 0 increased with age. MFS benefit with APA was highly significant for all age subgroups (Table). In pts ≥ 75 y, MFS risk with APA vs PBO was reduced by 59%; MFS risk was reduced by 86% and 76% for pts < 65 and 65-74 y, respectively. Risk of PFS2 with APA vs PBO was reduced across all age subgroups. PFS2 in pts < 65, 65-74, and ≥ 75 y: HR, 0.09 (p < 0.0001); HR, 0.56 (p = 0.0343); HR, 0.59 (p = 0.0092), respectively. Risk of symptomatic progression was lessened with APA vs PBO for all age subgroups (Table). There was a similar increase in incidence of tx-emergent adverse events (TEAE) with age in both tx arms that remained higher with APA. Incidence of grade 3/4 TEAE (≥ 75 vs < 65 y): APA, 50% vs 37%; PBO, 37% vs 28%. Conclusions: Pts in all age subgroups with high-risk nmCRPC had significant improvement in MFS with APA + ongoing ADT. The safety profile of APA was similar across age subgroups. Clinical trial information: NCT01946204. [Table: see text]

213O - Efficacy and safety of apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) from SPARTAN: Asian subpopulation

213O - Efficacy and safety of apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) from SPARTAN: Asian subpopulation

Phase Ib study of apalutamide (APA) with abiraterone acetate (AA) and prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Update on safety and efficacy.

173 Background: APA and AA target the androgenreceptor (AR) axis via different mechanisms and may have complementary activity in mCRPC. APA is an advanced AR antagonist that targets the AR ligand-binding domain with high affinity (Clegg. Cancer Res. 2012). APA prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets. This phase 1b study evaluates potential PK interactions between APA and AA + P. Here we report antitumor activity and safety of APA in combination with AA + P from 57 pts versus 29 pts presented at ASCO 2015 (NCT02123758). Methods: Pts with progressive mCRPC and ECOG PS ≤ 2 received AA (1000 mg/d) + P (5 mg BID) on Cycle 1 Day 1 (C1D1) with addition of APA (240 mg/d) on C1D8 in 28-day treatment (tmt) cycles. Efficacy assessment was based on RECIST 1.1 and PCWG2 criteria. Results: 57 pts started tmt on study; median tmt duration was 17 weeks. Median age was 70 years (range, 49-89) and median baseline PSA was 111 µg/L (range, 4-2597). Bone, nodal, and visceral disease were present in 50 (88%), 31 (54%), and 17 (30%) pts, respectively. 29 (51%), 29 (51%), and 23 (40%) pts were previously treated with a taxane, AA, or enzalutamide (ENZ), respectively. 47 pts discontinued tmt: disease progression (n = 39), consent withdrawal (n = 3), physician decision (n = 1), death (n = 1), and other (n = 3). In AA- and ENZ-naïve pts (n = 18), 67% had PSA decline ≥ 50%. In AA- or ENZ-treated pts (n = 39), 15% had PSA decline ≥ 50%. Most commonly reported ( > 10% of pts) drug-related AEs: fatigue (42%), diarrhea (21%), vomiting (21%), nausea (19%), hypokalemia (19%), decreased appetite (16%), hot flush (12%), abdominal pain (12%), and dysgeusia (11%). Grade ≥ 3 drug-related AEs reported in > 1 pt: fatigue (7%), hypokalemia (3.5%), hyponatremia (3.5%), and hypertension (3.5%). 1 pt discontinued study drug for grade 3 fatigue. Conclusions: Interim data indicate that 240 mg/d of APA with 1000 mg/d of AA + P has antitumor activity and an acceptable safety profile in mCRPC. Clinical trial information: NCT02123758. [Table: see text]

Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort

BackgroundApalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets. ObjectiveTo evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). Design, setting, and participantsWe conducted a multicenter phase 2 study of nmCRPC patients with a high risk for progression (prostate-specific antigen [PSA] ≥8 ng/ml or PSA doubling time [PSA DT] ≤10 mo). InterventionPatients received 240mg/d apalutamide while continuing on androgen-deprivation therapy. Outcome measurements and statistical analysisPrimary end point was 12-wk PSA response (Prostate Cancer Working Group 2 criteria). Secondary end points included safety, time to PSA progression (TTPP), and metastasis-free survival (MFS). Results and limitationsA total of 51 patients were enrolled; four patients with metastatic disease were excluded from the efficacy analysis. Patient characteristics included median age, 71 yr; Eastern Cooperative Oncology Group performance status 0 (76%); Gleason score ≤7 (57%); median PSA 10.7 ng/ml; and PSA DT ≤10 mo (45%). At median follow-up of 28.0 mo, 18 patients (35%) remained in the study. Overall, 89% of patients had ≥50% PSA decline at 12 wk. Median TTPP was 24.0 mo (95% confidence interval [CI], 16.3 mo–not reached [NR]); median MFS was NR (95% CI, 33.4 mo–NR). Most of the patients discontinued study treatment (n=33) due to disease progression (n=11 [22%]) or adverse events (AEs) (n=9 [18%]). The most common AE was fatigue (any grade, n=31 [61%]) although grade ≥3 fatigue was uncommon (n=2 [4%]). These represent the first apalutamide nmCRPC patient clinical data. ConclusionsIn high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control. Patient summaryAntitumor activity and the safety of apalutamide in patients with nonmetastatic castration-resistant prostate cancer support continued development in this setting. Trial registrationClinicalTrials.gov identifier NCT01171898