Researchers tested the androgen receptor inhibitor apalutamide plus ADT in patients with metastatic castration-sensitive prostate cancer.
CHICAGO-Patients with metastatic castration-sensitive prostate cancer (CSPC) who received a combination of the androgen receptor inhibitor apalutamide and androgen deprivation therapy (ADT) experienced improved radiographic progression–free survival (PFS) and overall survival (OS) compared with patients who received a placebo plus ADT.
The results of the TITAN study (abstract 5006), a phase III multinational, double-blind, randomized study, were presented by Kim N. Chi, MD, of the BC Cancer Agency in Vancouver, at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
“Apalutamide is a next-generation androgen receptor inhibitor approved in the United States and European Union for patients with nonmetastatic castration-resistant prostate cancer,” said Chi during his presentation. “The rationale behind the TITAN study was that direct inhibition of the androgen receptor by apalutamide may provide a more complete reduction of androgen signaling than ADT alone, leading to improved clinical outcomes.”
The primary endpoints of the TITAN study were radiographic PFS and OS. The secondary endpoints were time to initiation of cytotoxic chemotherapy, pain progression, chronic opioid use, and any skeletal-related events.
In total, 1,052 patients (median age, 68 years) with metastatic CSPC were randomized to the apalutamide arm (n = 525) or the placebo arm (n = 527). Patients on apalutamide received 240 mg per day in addition to ADT in 28-day cycles. Patients who had received prior treatment for localized disease (8%) or prior docetaxel (11%) for metastatic CSPC were allowed to participate. Overall, 63% and 37% of patients had high- or low-volume disease, respectively.
At a median follow-up of 22.6 months, 66% of patients in the apalutamide arm and 46% of patients in the placebo arm continued with their respective treatment. Apalutamide improved radiographic PFS (hazard ratio [HR], 0.48; 95% CI, 0.39–0.60; P < .0001), reducing the risk of progression or death by 52%. This improvement was observed in all subgroups analyzed. Apalutamide also improved overall survival, reducing the risk of death by 33% (HR, 0.67; 95% CI, 0.51–0.89; P = .0053).
For the secondary endpoints, the time to initiation of cytotoxic chemotherapy was significantly improved with apalutamide (HR, 0.39; 95% CI, 0.27–0.56; P < .0001).
The rates of grade 3/4 adverse events were similar between the treatments (42% on apalutamide vs 41% on placebo). Few patients in either group discontinued treatment due to adverse events (8% on apalutamide vs 5% on placebo). The primary adverse effect associated with apalutamide treatment was rash (all grades, 21.1% and ≥ grade 3, 6.3% in the in the treatment group vs 8.5% and 0.6%, respectively, in the placebo group).
Based on the study results, the independent data monitoring committee recommended unblinding to allow patients in the placebo group to cross over and receive apalutamide.
“ADT and apalutamide for metastatic hormone-sensitive prostate cancer improves survival and thus reinforces the current standard of ADT plus a single agent, whether it be docetaxel, abiraterone, enzalutamide, and now apalutamide,” said Michael Carducci, MD, of the Sidney Kimmel Cancer Center at Johns Hopkins in Baltimore.