An orally administered next-generation androgen receptor inhibitor with antitumor activity in CRPC.
Approved used the endpont of metastasis free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment.
Trade name Erleada.
Apalutamide significantly improved median metastasis-free survival by 2 years in men with nonmetastatic castrate-resistant prostate cancer (nmCRPC).
There are no presently approved therapies for patients with nmCRPC.
The prevention of metastases represents an important, unmet medical need.
In the SPARTAN trial, a phase 3, double-blind, randomized study of apalutamide versus placebo in patients with nonmetastatic castrate resistant prostate cancer.
SPARTANIII trial demonstrated a median metastasis free survival of 40.5 months compared with 16.2 months in the placebo arm.
Patients with nmCRPC and prostate-specific antigen doubling time (PSADT) of 10 months or less were randomized 2:1 to be administered 240 mg once daily of apalutamide or placebo on a continuous dosing daily regimen.
Results showed that apalutamide reduced the risk of distant metastasis or death by 72% with a median metastatic free survival of 40.5 months for the apalutamide cohort versus 16.2 months for the placebo group.
There was a 73% risk reduction in time to metastasis, a 71% risk reduction in progression free survival and a 55% risk reduction in symptomatic progression.
Data suggest that apalutamide should be considered as a new standard of care for men with high-risk nmCRPC.
In the TITAN study patients with metastatic, castration sensitive prostate cancer, the overall survival and radiographic progression-free survival was significantly longer with the addition of apalutamide and androgen deprivation therapy than with placebo plus androgen deprivation therapy (Chi, K).
Side effects include:fatigue, hypertension, rash, diarrhea, nausea, weight loss, arthralgia hot flashes, anorexia, fractures, peipheral edema and seizures with falls.
250 mg/day dose.
Trying to determine whether combining two androgen receptor inhibitor agents together- one that diminishes testosterone production and one that targets the androgen receptor would lead to better outcome than one agent alone.
The combination reduced the risks of progression by 31%.
A 7.4 months improvement in radiographic progression-free survival.
PSA declines reaching to undetectable levels of below 0.2, which was statistically improved with the combination over abiraterone alone.
Patients with visceral disease, either lung, liver, or adrenal, seemed to have even more benefit, in terms of radiographic progression-free survival and overall survival.
In patients over 75 years old, this improvement in overall survival turned out to be statistically significant by reducing the risk of death by 25%.
The overall findings of the ACIS trial: the combination of abiraterone-prednisone plus apalutamide might improve the primary endpoint of radiographic progression free survival, but did not improve the secondary endpoints of overall survival, time to initiation of cytotoxic chemotherapy, time to chronic opioid use, or time to pain progression.