Enzalutamide in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study

Abstract

Introduction Enzalutamide significantly improved clinical outcomes compared with placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) with disease progression despite androgen deprivation therapy (ADT) in the PREVAIL study. However, few patients from Asia were enrolled. Our study (NCT02294461) aimed to evaluate the safety and efficacy of enzalutamide in this disease setting in patients in mainland China, Korea, Taiwan, and Hong Kong. Methods In this double-blind, phase III study, patients with asymptomatic/mildly symptomatic metastatic prostate cancer and disease progression despite ADT were randomized to enzalutamide (160 mg/day) or placebo. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included overall survival, radiographic progression-free survival, time to first skeletal-related event (SRE), time to initiation of cytotoxic chemotherapy, PSA response ≥ 50%, best overall soft-tissue response, and safety. Pre-planned interim analysis was scheduled following approximately 175 PSA-progression events (67% of targeted total of 261 events). An additional 5-year landmark analysis of overall survival, time to antineoplastic therapy, and safety was performed. Results The double-blind study period was stopped after interim analysis owing to the benefit of enzalutamide over placebo. Overall, 388 patients were randomized (enzalutamide, n = 198; placebo, n = 190). Baseline characteristics were balanced between treatment groups. Enzalutamide significantly reduced risk of PSA progression vs placebo (hazard ratio 0.38; 95% CI 0.27–0.52; P < 0.0001). Median time to PSA progression was 8.31 months with enzalutamide and 2.86 months with placebo. Secondary endpoints, including 5-year overall survival, were significantly improved with enzalutamide, except time to first SRE. Adverse-event incidence was similar between enzalutamide and placebo. Fatigue was the most common drug-related adverse event in both treatment groups. Conclusion Enzalutamide significantly reduced risk of PSA progression, improved secondary efficacy endpoints, and was well tolerated in chemotherapy-naïve Asian patients with mCRPC with disease progression despite ADT. Trial Registration www.clinicaltrials.gov NCT02294461. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02140-2.

Evaluating first-line therapeutic strategies for metastatic castration-resistant prostate cancer: a comprehensive network meta-analysis and systematic review

“…The analysis included seven multicenter RCTs, predominantly phase III first-line treatments, with the exception of one phase IV second-line treatment RCT included for network completeness ( 10 – 16 ). These trials spanned 2015 to 2020, involving a total of 6,411 participants.…”

Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer

“…Data from 24 eligible RCTs (n = 22 166) were included (Figure 1); M0 HSPC (3 RCTs, n = 2171), M1 HSPC (9 RCTs, n = 8994), M0 CRPC (3 RCTs, n = 4256), M1 CRPC (9 RCTs, n = 6745) . One study had patients spanning different disease states, so these populations were split for analysis according to their separate publications .…”

“…Studies investigated SOC used with ARSI monotherapy or combined with another ARSI or docetaxel. The following agents were combined with SOC therapy: abiraterone acetate and prednisolone (herein referred to as abiraterone acetate) (n = 9), abiraterone acetate and docetaxel (n = 1), enzalutamide alone (n = 9), abiraterone acetate and enzalutamide (n = 2), darolutamide alone (n = 1), darolutamide and docetaxel (n = 1), and apalutamide alone (n = 2) were studied. Of the 24 eligible studies, 18 reported CV events (75%): only 16 reported grade 3 or higher CV events (67%).…”

Association of Second-generation Antiandrogens With Cognitive and Functional Toxic Effects in Randomized Clinical Trials

“…There were 22 studies that underwent full-text review, of which 10 studies were excluded, as specified in Figure 1. Details of the 12 studies comprising 13 524 participants included in our systematic review and their reported relevant toxic effects are summarized in the Table [21][22][23][24][25][26][27][28][29][30][31][32] and in eTable 1 in Supplement 1. All studies were multinational, with data collection ranging from 2008 to 2021.…”