Apalutamide in Patients with High Burden of Metastatic Hormone-sensitive Prostate Cancer: A Subgroup Analysis of TITAN.

Background and objective: A post hoc analysis of TITAN evaluated the clinical benefit of apalutamide plus androgen-deprivation therapy (ADT) versus ADT alone in metastatic hormone-sensitive prostate cancer (mHSPC) with high disease burden.

Methods: Patients were assessed in subgroups of those with four to fewer than ten, ten to <20, or ≥20 bone metastases; with lung but not liver metastases; and with no/mild or moderate/severe pain at baseline. Prostate-specific antigen (PSA) response, overall survival (OS), other endpoints, and safety were assessed using descriptive statistics, Kaplan-Meier method, and Cox proportional hazard model.

Key findings and limitations: Higher proportions of patients receiving apalutamide than those receiving placebo achieved a deep PSA response of ≤0.2 ng/ml at 3, 6, and 12 mo of treatment initiation regardless of the disease burden. OS benefit favored apalutamide plus ADT versus ADT alone in all bone metastasis subgroups: four to fewer than ten (hazard ratio [HR]: 0.68 [95% confidence interval 0.44-1.03]; p = 0.07), ten to <20 (0.61 [0.37-1.00]; p = 0.048), or ≥20 (0.53 [0.39-0.72]; p < 0.001) bone metastases. Addition of apalutamide to ADT was beneficial across other endpoints and in patients with lung but no liver metastases and regardless of pain at baseline. No new safety signals were observed across subgroups.

Conclusions and clinical implications: These findings provide strong evidence for early intensification with apalutamide plus ADT in patients with mHSPC regardless of the disease burden.