Phase III TITAN study of Erleada shows improved PFS and OS in prostate cancer.

The Janssen Pharmaceutical Companies of Johnson & Johnson announced findings from the investigational Phase III TITAN study, which showed the addition of Erleada (apalutamide) 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. Erleada plus ADT significantly extended OS compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95 percent CI, 0.51-0.89; P=0.0053). Erleada plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95 percent CI, 0.39-0.60; P<0.0001).

The two-year OS rates, after a median follow-up of 22.7 months, were 82 percent for Erleada plus ADT compared to 74 percent for placebo plus ADT. These data formed the basis of a supplemental New Drug Application (sNDA) to the FDA seeking 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. 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 Erleada plus ADT was also met, with a 61 percent risk reduction compared with placebo plus ADT (HR=0.39; 95 percent CI, 0.27-0.56; P<0.0001).

In exploratory endpoints, median time to PSA progression was more favorable following Erleada plus ADT, compared with placebo plus ADT, and prostate-specific antigen (PSA) reached undetectable levels in 68 percent of patients in the Erleada plus ADT arm and 29 percent of patients in the placebo plus ADT arm. Additionally, Erleada plus ADT, compared with placebo plus ADT, achieved a 34 percent 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 percent 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 Erleada safety profile. Results were presented in an oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published online in The New England Journal of Medicine.