Apalutamide 60mg tablets

BackgroundWithin the last 10 years, multiple clinical randomized controlled trials in metastatic castration-sensitive prostate cancer patients (mCSPC) have demonstrated that androgen deprivation therapy (ADT) combination therapy is significantly superior to ADT alone. However, there are no guidelines that recommend the best clinical decisions with regard to multi-selective systemic therapy for mCSPC.MethodsTwo independent researchers have conducted a systematic literature search of the Cochrane Central, Web of Science, Clinical Trials. gov and EU Clinical Trial Register databases with a search deadline of July 5, 2022. Hazard Ratio (HR) and 95% confidence intervals were analyzed and extracted for overall and progression-free survival and their subgroups, as well as the number of adverse events. Trial quality was assessed through the Risk of Bias Form and the Newcastle-Ottawa Scale, and systematic reviews and meta-analyses were carried out in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) project.Results8704 patients from 7 studies participated in trials comparing the effectiveness of 4 ADT combination treatments (including ADT + docetaxel, ADT + abiraterone acetate, ADT + enzalutamide, ADT + apalutamide) and ADT alone (ADT + placebo/no-treatment). The results suggested that ADT combination therapy was significantly better than ADT alone. Furthermore, based on the patient's initial clinical characteristics and expected prognosis, we tentatively provided relevant optimal treatment options.ConclusionsADT + ARAT outperformed ADT ± docetaxel in OS/PFS for mCSPC, with strategies tailored to patient profiles. Future work will leverage advanced analytics and standardized reporting; direct combination trials are critical for precise guidance.

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Aim: Recent network meta-analyses (NMAs) in metastatic castration-sensitive prostate cancer have not adequately addressed potential treatment effect modifiers and population imbalances, which introduces bias. Although, individual-patient data (IPD) are seldom available across all trials, recent methodological advances allow adjustments using a combination of IPD and aggregate data. Materials & methods: IPD from the ARASENS trial (darolutamide + docetaxel + androgen-deprivation-therapy [ADT]) and aggregate data from a systematic review were analyzed. Two methods were used to adjust for population imbalances: multilevel network meta-regression (ML-NMR) using baseline characteristics, and network meta-interpolation (NMI) using subgroup data. Relative effects were estimated for an ARASENS-like population, with sensitivity analysis in an average trial population. Results: Twelve studies, including ARASENS, were included. All studies reported baseline characteristics for ML-NMR. Sufficient subgroup data for NMI were available in 8/12 studies for overall survival (OS) and 5/12 studies for progression-free survival (PFS). Darolutamide + docetaxel + ADT showed significant benefit over docetaxel + ADT, ADT and standard-nonsteroidal-antiandrogen + ADT in all analyses. ML-NMR showed improved OS for darolutamide + docetaxel + ADT compared with abiraterone + docetaxel + ADT, apalutamide + ADT, enzalutamide + ADT and abiraterone + ADT. ML-NMR also showed improved PFS for darolutamide + docetaxel + ADT compared with apalutamide + ADT and enzalutamide + ADT. Using NMI, darolutamide + docetaxel + ADT demonstrated OS benefit over abiraterone + ADT and PFS benefit relative to abiraterone + ADT and apalutamide + ADT. Findings were consistent in an average population, although ML-NMR did not show significant OS benefit of darolutamide + docetaxel + ADT over apalutamide+ADT. Conclusion: Improved outcomes were observedwith darolutamide+docetaxel+ADT compared with other therapies. By incorporating effect modifiers and addressing population imbalances, we provide clinicians with a more accurate understanding of treatment efficacy for better-informed decision-making.

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ObjectiveAndrogen receptor pathway inhibitors (ARPIs) are cornerstone treatments for advanced prostate cancer; however, their potential to increase fall risk remains a significant clinical concern. This meta-analysis aims to provide a rigorous, drug-specific evaluation of the association between novel ARPIs and the risk of falls.MethodsWe systematically searched PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov for Phase 2 or 3 randomized controlled trials (RCTs) comparing ARPIs (enzalutamide, apalutamide, and darolutamide) with control groups (placebo or non-steroidal antiandrogens [NSAA]). The primary outcomes were risk ratios (RRs) for all-grade and grade ≥ 3 falls. To account for multiplicity across correlated outcomes and the limited number of studies, pooled RRs were estimated using random-effects models with the restricted maximum-likelihood (REML) method. All analyses were performed on a logarithmically transformed scale, with 97.5% confidence intervals (CIs). Prediction intervals (PIs) were calculated to assess the dispersion of effects. Subgroup analyses were stratified by specific ARPI agents, control types, and clinical stages.ResultsEleven RCTs involving 12,239 patients were included. Overall, ARPIs were significantly associated with the increased risk of all-grade falls (RR 2.00, 97.5% CI 1.46-2.73, P 2 = 77.6%; PI 0.67-5.99) and grade ≥ 3 falls (RR 2.15, 97.5% CI 1.32-3.52, P = 0.0008, I2 = 0%; PI 1.15-4.02). However, risk profiles varied substantially across individual agents. Enzalutamide was associated with the highest risk increase (RR 2.55 vs. placebo, 97.5% CI 1.62-4.01, I2 = 79.2%; RR 2.47 vs. NSAA, 97.5% CI 1.14-5.37, I2 = 71.8%), followed by apalutamide (RR 1.65, 97.5% CI 0.77-3.52, I2 = 87.2%). In contrast, darolutamide demonstrated a favorable safety profile with no statistically significant increase in the risk of all-grade falls (RR 1.25, 97.5% CI 0.87-1.79, I2 = 0%) or severe falls (RR 1.31, 97.5% CI 0.34-5.00).ConclusionsCurrent evidence indicates that the increased risk of falls associated with ARPI therapy varies significantly among individual agents, rather than being a uniform class effect. While enzalutamide and apalutamide are statistically associated with elevated fall risk, darolutamide appears to maintain a more favorable safety profile. However, these drug-specific comparisons remain exploratory due to subgroup imbalances. Clinicians should consider proactive fall-risk assessments and individualized treatment selection, particularly for elderly or frail populations.

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BackgroundPharmacokinetic studies suggest that specific prostate cancer therapies may alter the metabolism of direct oral anticoagulants (DOACs), leading to elevated risks of thrombosis or bleeding.MethodsTo assess the risk of thrombosis or bleeding, population-based, retrospective, parallel analyses were conducted in Ontario and Alberta, Canada, among adults patients with prostate cancer who were prescribed a DOAC and a potentially interacting androgen receptor pathway inhibitor (including enzalutamide, apalutamide, or abiraterone) compared with non-DOACs between 2012 and 2023. Analyses were stratified based on a DOAC-inducer cohort (enzalutamide or apalutamide, which might increase the risk of thrombosis) and a DOAC-inhibitor cohort (abiraterone, which might increase the risk of bleeding). Overlap weighted Cox proportional hazard models accounting for 37 covariates were performed independently in each jurisdiction and were pooled using random-effects meta-analysis.ResultsIn total, 2997 individuals were included (2107 from Ontario and 890 from Alberta). In patients who received enzalutamide or apalutamide, there was no increased risk of all thrombosis in the DOAC groups compared with the non-DOAC groups (pooled hazard ratio, 0.83; 95% confidence interval, 0.36-1.93). In patients who received abiraterone, no significant differences were observed in any bleeding events comparing the DOAC and non-DOAC groups (pooled hazard ratio, 1.16; 95% confidence interval, 0.10-13.99). The results were consistent in multiple sensitivity analyses.ConclusionsThe concurrent use of enzalutamide, apalutamide, or abiraterone with DOACs did not contribute to clinically meaningful changes in the risk of thrombosis or bleeding in individuals with prostate cancer.

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BackgroundThe last decade saw the emergence of several new systemic therapies for metastatic hormone-sensitive prostate cancer (mHSPC). While these treatments demonstrated similar efficacy in indirect comparisons, comparisons of safety outcomes are needed to help guide the selection of treatment regimens and sequences. We conducted network meta-analyses (NMAs) comparing safety of systemic treatments for mHSPC.MethodsA systematic literature review was performed for randomized controlled trials (RCTs) investigating systemic treatments for mHSPC published before July 2022. Studies were restricted by network connectivity and study population homogeneity. Bayesian NMAs were performed for available data on grade ≥3 adverse events (AEs), serious AEs (SAEs), and any AE.ResultsThe study included eight RCTs (n=172-1228 by treatment arm) and seven treatment regimens: androgen deprivation therapy (ADT) alone, docetaxel plus ADT, androgen receptor pathway inhibitor (ARPI; apalutamide, enzalutamide, or abiraterone acetate plus prednisone [AAP]) plus ADT, and docetaxel plus ARPI (darolutamide or AAP) plus ADT. Apalutamide plus ADT had the lowest relative risk ([RR]; 1.18 (95% credible interval [CrI] 1.02-1.35) of grade ≥3 AEs versus ADT alone, followed by enzalutamide plus ADT (1.34 [1.17-1.52]), docetaxel plus ADT (1.44 [1.33-1.56]), AAP plus ADT (1.48 [1.39-1.58]), darolutamide plus docetaxel plus ADT (1.53 [1.33-1.72]), and AAP plus docetaxel plus ADT (1.60 [1.41-1.79]). For SAEs, RRs (95% CrI) versus ADT alone were 1.26 (1.03-1.53) for apalutamide plus ADT, 1.33 (1.12-1.57) for AAP plus ADT, 1.54 (1.28-1.84) for enzalutamide plus ADT, 3.78 (3.35-4.26) for docetaxel plus ADT, and 3.83 (3.39-4.31) for darolutamide plus docetaxel plus ADT. Similar results were observed for any AE.ConclusionsOverall, risk of grade ≥3 AEs, SAEs, and any AE was lower with doublet ARPI versus docetaxel-based doublet or triplet regimens, and apalutamide plus ADT had the lowest risk. Variability of data reporting should be considered.

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