Apalutamide Compared with Darolutamide for the Treatment of Non-metastatic Castration-Resistant Prostate Cancer: Efficacy and Tolerability in a Matching-Adjusted Indirect Comparison

Abstract

Introduction: Apalutamide 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.

Methods: This 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.

Results: Before 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.

Conclusion: This 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 registration: ARAMIS ClinicalTrials.gov number: NCT02200614; SPARTAN ClinicalTrials.gov number: NCT01946204.

Keywords: Androgen deprivation therapy; Apalutamide; Darolutamide; Non-metastatic castration-resistant prostate cancer; Oncology.

© 2021. The Author(s).

Figures

Fig. 1

Posterior distribution of hazard ratio of a metastasis-free survival, b progression-free survival, c prostate-specific antigen progression, and d overall survival at the first interim analyses among patients of the SPARTAN study versus ARAMIS study. A hazard ratio (HR) or odds ratio (OR) below 1 favors APA + ADT and a value above 1 favors DARO + ADT. Solid curves show the matching-adjusted indirect comparison after reweighting of patient-level data in SPARTAN, using aggregate-level data from ARAMIS. Dashed curves show original SPARTAN data versus ARAMIS data. ADT androgen deprivation therapy; CrI credible interval; MFS metastasis-free survival; OS overall survival; PFS progression-free survival; PSA prostate-specific antigen

Fig. 2

Posterior distribution of hazard ratio of adverse events, and serious adverse events among patients of the SPARTAN study versus ARAMIS study. A hazard ratio (HR) or odds ratio (OR) below 1 favors APA + ADT and a value above 1 favors DARO + ADT. Solid curves show the matching-adjusted indirect comparison after reweighting of patient-level data in SPARTAN, using aggregate-level data from ARAMIS. Dashed curves show original SPARTAN data versus ARAMIS data. AE adverse event; CrI credible interval; SAE serious adverse events