Dataset Information

Darolutamide For Castration-Resistant Prostate Cancer.

ABSTRACT: The treatment landscape of advanced prostate cancer continues to evolve rapidly, with newer and more active drugs being used in earlier phases of the disease based on improved overall survival. After adoption of docetaxel for metastatic castration-sensitive disease, large trials with next-generation androgen receptor-signaling inhibitors (abiraterone, enzalutamide and apalutamide) have demonstrate significant improvements in survival and important secondary endpoints. For non-metastatic castration-resistant prostate cancer, recent phase III placebo-controlled trials with enzalutamide, apalutamide and darolutamide all demonstrated benefits in improving metastasis-free survival. This review aims to summarize the clinical development of darolutamide, a novel next-generation androgen receptor antagonist, including preclinical data, clinical studies and the potential of darolutamide for the treatment of advanced prostate cancer. To date, darolutamide efficacy and tolerability has been demonstrated in the ARAMIS trial, which demonstrated an improvement in metastasis-free survival compared to placebo for non-metastatic castration-resistant prostate cancer patients with a rapid PSA doubling time. Ongoing studies will further evaluate the role of darolutamide in metastatic castration-sensitive prostate cancer in combination with docetaxel (ARASENS trial) and also in other stages of the disease.

SUBMITTER: Bastos DA

PROVIDER: S-EPMC6816030 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Darolutamide For Castration-Resistant Prostate Cancer.

Bastos Diogo A DA Antonarakis Emmanuel S ES

OncoTargets and therapy 20191023

The treatment landscape of advanced prostate cancer continues to evolve rapidly, with newer and more active drugs being used in earlier phases of the disease based on improved overall survival. After adoption of docetaxel for metastatic castration-sensitive disease, large trials with next-generation androgen receptor-signaling inhibitors (abiraterone, enzalutamide and apalutamide) have demonstrate significant improvements in survival and important secondary endpoints. For non-metastatic castrati ...[more]

PMID: 31695432

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Project description:IntroductionApalutamide and darolutamide are next-generation androgen receptor inhibitors that have demonstrated superior efficacy compared to placebo in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen deprivation therapy (ADT). In the absence of head-to-head studies, the present study sought to indirectly compare the efficacy and tolerability between these two treatments.MethodsThis anchored matching-adjusted indirect comparison (MAIC) used patient-level data from the phase 3, randomized, controlled SPARTAN study (apalutamide + ADT), weighted to match aggregate published data from the ARAMIS study (darolutamide + ADT) for clinically relevant baseline measures. Hazard ratios (HR) and 95% credible intervals (CrI) were estimated for efficacy endpoints: metastasis-free survival (MFS), prostate-specific antigen (PSA) progression, progression-free survival (PFS), and overall survival (OS). Odds ratios were estimated for tolerability outcomes: adverse events and serious adverse events.ResultsBefore weighting, baseline characteristics from SPARTAN versus ARAMIS were different for median PSA (7.8 vs. 9.2 ng/mL), Eastern Cooperative Oncology Group performance status of 1 (23% vs. 31%), use of bone-targeted agents (10% vs. 4%), median time from initial diagnosis (94.9 vs. 85.4 months), and proportion of patients from North America (35% vs. 12%) and Europe (50% vs. 64%). After matching (n = 455), our analysis demonstrated that apalutamide + ADT had a Bayesian probability of being more effective than darolutamide + ADT for MFS [98.3%; HR 0.70 (95% CrI 0.51, 0.98)], PSA progression [~ 100%; HR 0.46 (95% CrI 0.33, 0.64)], and PFS [93.2%; HR 0.79 (95% CrI 0.59, 1.08)]. Results for OS and tolerability were similar between apalutamide + ADT and darolutamide + ADT.ConclusionThis anchored MAIC analysis of pivotal phase 3 studies in patients with nmCRPC suggests that apalutamide + ADT is more effective than darolutamide + ADT for MFS, progression-free survival (PFS), and prostate-specific antigen (PSA) progression, with a similar OS benefit and tolerability profile.Trial registrationARAMIS ClinicalTrials.gov number: NCT02200614; SPARTAN ClinicalTrials.gov number: NCT01946204.

Dataset Information

Darolutamide For Castration-Resistant Prostate Cancer.

Publications

Darolutamide For Castration-Resistant Prostate Cancer.

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