Results from the phase 3 TITAN study were presented in an oral session at the American Society of Clinical Oncology (ASCO ) Annual Meeting in Chicago, and simultaneously published in The New England Journal of Medicine ( NEJM ).
Research has shown the addition of Apalutamide ( Erleada ) to androgen deprivation therapy ( ADT ) compared with placebo plus ADT significantly improved the dual primary endpoints of overall survival ( OS ) and radiographic progression-free survival ( rPFS ) in patients with metastatic castration-sensitive prostate cancer ( mCSPC ).
The study included patients with mCSPC regardless of extent of disease or prior Docetaxel treatment history.
Apalutamide plus ADT significantly extended overall survival compared to placebo plus ADT with a 33% reduction in the risk of death ( HR=0.67; 95% CI, 0.51-0.89; P=0.0053 ).
Apalutamide plus ADT also significantly improved rPFS 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 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 data formed the basis of a supplemental New Drug Application ( sNDA ) to the U.S. Food and Drug Administration ( FDA ) for approval of a new indication for Erleada for the treatment of patients with mCSPC, which is currently under review through the Real-Time Oncology Review ( RTOR ) program.
Patients with metastatic castration-sensitive prostate cancer typically have a poor prognosis, with a median overall survival of less than five years.
These data suggest that Apalutamide prolongs overall survival and delays disease progression in patients with metastatic castration-sensitive prostate cancer.
In addition to meeting the primary dual endpoints of OS and rPFS, the secondary endpoint of prolonged time to cytotoxic chemotherapy in patients treated with Apalutamide plus ADT was also met, with a 61% risk reduction compared with placebo plus ADT ( HR=0.39; 95% CI, 0.27-0.56; P less than 0.0001 ).
In exploratory endpoints, median time to PSA progression was more favorable following Apalutamide plus ADT, compared with placebo plus ADT, and prostate-specific antigen ( PSA ) reached undetectable levels in 68% of patients in the Apalutamide plus ADT arm and 29% of patients in the placebo plus ADT arm.
Additionally, Apalutamide plus ADT, compared with placebo plus ADT, achieved a 34% risk reduction in median time to second progression-free survival ( PFS2 ), defined as time from randomization to either disease progression on first subsequent anticancer therapy or death, whichever occurred first ( HR=0.66; 95% CI, 0.50-0.87 ).
Although time to pain progression was tested, it did not reach statistical significance.
Due to a hierarchical statistical design, no formal testing for further secondary endpoints, including median time to chronic opioid use and median time to skeletal-related events, were conducted at this time.
Adverse events were generally consistent with the known Apalutamide safety profile. The most common grade 3/4 adverse events for Apalutamide plus ADT, versus placebo plus ADT were similar ( 42% vs. 41% ).
The most common grade 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% ).
Additional reported grade 3 adverse effects for Apalutamide plus ADT versus placebo plus ADT were back pain ( 2.3% vs. 2.7% ), blood alkaline phosphatase increased ( 0.4% vs. 2.5% ) and anemia ( 1.7% vs. 3.2% ).
Treatment discontinuation due to adverse effects was 8% in the Apalutamide arm compared to 5% in the placebo arm.
Rash of any grade was more common among patients treated with Apalutamide plus ADT, versus placebo plus ADT ( 27% vs. 9%, respectively ).
TITAN is a phase 3 randomized, placebo-controlled, double-blind study in men with mCSPC regardless of extent of disease or prior Docetaxel treatment history.
The study included 1,052 patients included 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 mCSPC were randomized 1:1 and received either Apalutamide ( 240 mg ) plus continuous 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 mCSPC 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 mCSPC.
Participants were treated until disease progression or the occurrence of unacceptable treatment-related toxicity.
Dual primary endpoints of the study were OS and rPFS. 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 PFS2 and time to symptomatic progression.
Metastatic castration-sensitive prostate cancer refers to prostate cancer that still responds to ADT and has spread to other parts of the body.
Patients with mCSPC 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, 2019