The European Commission ( EC ) has granted marketing authorisation for the expanded use of Erleada ( Apalutamide ) to include the treatment of adult men with metastatic hormone-sensitive prostate cancer ( mHSPC ) in combination with androgen deprivation therapy ( ADT ).
The EC approval is based on data from the phase 3 TITAN study, which assessed the addition of Apalutamide to ADT in a broad range of patients with mHSPC, regardless of disease volume, prior treatment with docetaxel or staging at initial diagnosis.
The dual primary endpoints of the study were overall survival ( OS ) and radiographic progression-free survival ( rPFS ).
Apalutamide plus ADT significantly improved overall survival compared to placebo plus ADT with a 33% reduction in the risk of death ( hazard ratio, HR=0.67; 95% CI, 0.51-0.89; p=0.0053 ).
In both study arms, median overall survival was not reached.
Apalutamide plus ADT has also significantly improved radiographic progression-free survival compared to placebo plus ADT with a 52% reduction in risk of radiographic progression or death compared to placebo plus ADT ( HR=0.48; 95% CI, 0.39-0.60; p less than 0.0001 ). The median radiographic progression-free survival was 22.1 months for placebo plus ADT and not reached for Apalutamide plus ADT.
The two-year overall survival rates, after a median follow up of 22.7 months, were 82% for Apalutamide plus ADT compared to 74% for placebo plus ADT.
These results were published in The New England Journal of Medicine.
The safety profile observed in the TITAN study for Apalutamide plus ADT was consistent with that described in previous studies.
In the study, 42% of patients on Apalutamide plus ADT experienced grade 3/4 adverse events, compared to 41% of patients on placebo plus ADT.
The most common grade greater than or equal to 3 adverse effects for Apalutamide plus ADT versus placebo plus ADT were hypertension ( 8.4% vs. 9.1% ) and skin rash ( 6.3% vs. 0.6% ).
Treatment discontinuation due to adverse effects was 8% in the Apalutamide arm compared to 5% in the placebo arm.
In Europe, Apalutamide is also approved for use in adults with non-metastatic castration-resistant prostate cancer ( nmCRPC ) who are at high risk of developing metastatic disease.
TITAN is a phase 3 randomised, placebo-controlled, double-blind study in men with mHSPC regardless of extent of disease or prior Docetaxel treatment history.
The study included 1,052 patients in intention-to-treat ( ITT ) population in 23 countries across 260 sites in North America, Latin America, South America, Europe and Asia Pacific.
Patients with mHSPC were randomised 1:1 and received either Apalutamide ( 240 mg ) plus continuous androgen deprivation therapy ( ADT ) ( n=525 ), or placebo plus ADT ( n=527 ).
The recruitment period for the study spanned from December 2015 to July 2017.
The study included a broad population of patients with mHSPC, including patients with both low- and high-volume disease, those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of Docetaxel or up to six months of ADT for mHSPC.
Participants were treated until disease progression or the occurrence of unacceptable treatment-related toxicity.
Dual primary endpoints of the study were overall survival and radiographic progression-free survival. Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use and time to skeletal-related event. Exploratory endpoints included time to PSA progression, time to second progression-free survival and time to symptomatic progression.
Metastatic hormone-sensitive prostate cancer, also referred to as metastatic castration sensitive prostate cancer ( mCSPC ), refers to prostate cancer that still responds to androgen deprivation therapy ( ADT ) and has spread to other parts of the body.
Patients with metastatic hormone-sensitive prostate cancer tend to have a poor prognosis, with a median overall survival of less than five years, underscoring the need for new treatment options. ( Xagena )
Source: Janssen, 2020