Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer

Abstract

BACKGROUNDApalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. METHODSIn this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. RESULTSA total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. CONCLUSIONSIn this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the sideeffect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.

Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines

“…The panel's recommendation was made irrespective of metastatic burden (86% consensus). Recent data from the ARCHES, ENZAMET, and TITAN studies suggest clinical benefit with enzalutamide and apalutamide in this setting as well 61–63 . US FDA approval for these agents in mHSPC is pending.…”

“…9 The panel felt that T levels should be ENZAMET, and TITAN studies suggest clinical benefit with enzalutamide and apalutamide in this setting as well. [61][62][63] US FDA approval for these agents in mHSPC is pending.…”

Novel agents for metastatic hormone‐sensitive prostate cancer – a practice guide for urologists

“…Distinct adverse reactions specific to apalutamide include rash (typically macular/maculopapular in appearance) and hypothyroidism. Apalutamide was also associated with increased ischaemic heart disease compared to placebo (4.4% vs 1.5%) .…”

“…Lastly, apalutamide is a non‐steroidal selective AR antagonist. The TITAN (a study of apalutamide (JNJ‐56021927, ARN‐509) plus ADT vs ADT in participants with mHSPC) trial reported that apalutamide combined with ADT reduced the risk of radiographic progression by 52% (HR 0.48, 95% CI 0.39–0.60) and risk of death by 33% (HR 0.67, 95% CI 0.51–0.89) . Distinct adverse reactions specific to apalutamide include rash (typically macular/maculopapular in appearance) and hypothyroidism.…”

Vorwort

“…Die Indikationserweiterung von Apalutamid (Erleada ® ) in Kombination mit einer Androgen-Deprivationstherapie (ADT) für die Therapie des mHSPC ist hier ein wichtiger Meilenstein. Apalutamid plus ADT zeigte in der Zulassungsstudie TITAN im Vergleich zur alleinigen ADT eine hohe Wirksamkeit bei gleichzeitig guter Verträglichkeit, ohne wesentliche Einbußen der Lebensqualität gegenüber alleiniger ADT (ermittelt anhand des Functional Assessment of Cancer Therapy-Prostate (FACT-P), explorativer Endpunkt) [2]. Entscheidend ist, dass dies für ein breites Spektrum an mHSPC-Patienten galt, d.h. unabhängig von bspw.…”