The development of apalutamide for the treatment of prostate cancer

Prostate cancer progresses, despite androgen-deprivation therapy, the backbone of its treatment. This progression is mainly related to the androgen receptor (AR)-related mechanisms of resistance, and, several AR-targeted therapies have demonstrated benefit in metastatic and nonmetastatic disease. Apalutamide is a third-generation AR-targeted therapy which competitively blocks the AR and prevents AR dimerization, nuclear internalization, thereby avoiding cancer progression. Early studies have demonstrated that apalutamide was safe and demonstrated clinical benefit. Phase II and phase III studies had confirmed preliminary results of clinical benefit with apalutamide in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and in metastatic hormone-sensitive prostate cancer (mHSPC).

Herein, the authors discuss the development of apalutamide, from its discovery and early studies to phase III trials. They also examine new perspectives and biomarkers that may help oncologists to make decisions in patients taking apalutamide. Studies evaluating apalutamide in other settings and in combination with other therapies are also debated.

Apalutamide has become a relevant therapy for patients with nmCRPC and mHSPC for its benefit in delaying metastasis in addition to its improvement of overall survival, without compromising the quality of life. Apalutamide should be considered as a standard-of-care for patients with nmCRPC and patients with mHSPC.