Apalutamide: Emerging Therapy for Non-Metastatic Castration-Resistant Prostate Cancer

Abstract

Prostate cancer is the second deadliest cancer in the US and the fourth most common cancer among Saudi males. Patients usually present with non-metastatic disease and treated with localized therapy. However, up to 40% of the patients will experience biochemical recurrence, within 10 years. Androgen deprivation therapy (ADT) is used in this setting to delay metastatic disease. Patients with high prostate-specific antigen (PSA), despite appropriate ADT, are diagnosed with castrate-resistant prostate cancer (CRPC). A subset of those patients will be presented with a shorter PSA doubling time (PSA-DT) ≤10 months. These patients are identified at higher risk for metastatic disease and death from prostate cancer, which represents a challenging dilemma where optimal management is unclear. Apalutamide was the first drug to get approved in the localized setting to delay metastatic disease from occurring. This review article will discuss the development, safety, and efficacy of apalutamide and its current place in therapy.

Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study

“…However, the median time-to-remission of the worst grade (Grade 3) of skin rash was 1.0 month. Therefore, even if some patients experienced several incidents of skin rash, the worst grade of skin rash remitted within 1.0 Apalutamide and N-desmethyl apalutamide are two major pharmacologically active components detected in the systemic circulation at steady-state [8,9]. The current integrated analysis showed that there was a possible correlation between plasma exposure to apalutamide and incidence of skin rash, but it did not significantly impact the grade of skin rash.…”

“…Apalutamide and N-desmethyl apalutamide are two major pharmacologically active components detected in the systemic circulation at steady-state [ 8 , 9 ]. The current integrated analysis showed that there was a possible correlation between plasma exposure to apalutamide and incidence of skin rash, but it did not significantly impact the grade of skin rash.…”

Ras and Wnt Interaction Contribute in Prostate Cancer Bone Metastasis

“…Conversely, activated AR and its cofactor FOXA1 inhibits TWEAK/Fn14/IKK-β activation through directly binding to an androgen-binding element in TWEAK and the Fn14 promoter/enhancer in order to reduce TWEAK and Fn14 transcription [22]. After androgen deprivation therapy (ADT), some castration-sensitive PCa cells will transit into CRPC cells, which is the beginning of PCa metastasis [24,25]. Izumi and Mizokami summarized the characteristic of C-C motif ligand 5 (CCL5) in regulating AR expression, in which CCL5 downregulates AR expression [26].…”

Skin Rash Following Administration of Apalutamide in Japanese Patients with Advanced Prostate Cancer: An Integrated Analysis of the Phase 3 SPARTAN and TITAN Studies and a Phase 1 Open-Label Study

“…Apalutamide and N-desmethyl apalutamide are two major pharmacologically active components detected in the systemic circulation at steady-state. [8,9] The current integrated analysis showed that there was a possible correlation between plasma exposure to apalutamide and incidence of skin rash, but it did not signi cantly impact the grade of skin rash. However, the results should be interpreted with caution due to the limited sample size.…”