In an analysis from the phase III TALAPRO-2 trial reported in The Lancet Oncology, Matsubara et al found that first-line talazoparib plus enzalutamide was associated with prolonged time to definitive deterioration in global health status/quality of life (GHS/QOL) vs placebo plus enzalutamide in patients with metastatic castration-resistant prostate cancer.
The primary analysis of the trial showed a significant improvement in radiographic progression–free survival with talazoparib/enzalutamide (hazard ratio [HR] = 0.63, P < .0001).
Study Details
In the double-blind trial, 805 patients with any homologous recombination repair status from sites in 26 countries were randomly assigned to receive talazoparib at 0.5 mg once daily or placebo plus enzalutamide at 160 mg once daily between January 2019 and September 2020; 395 patients assigned to talazoparib/enzalutamide and 398 assigned to placebo/enzalutamide were included in the patient-reported outcome population. Time to definitive deterioration in GHS/QOL on the EORTC Quality of Life Questionnaire (QLQ-C30) and other functional scales was defined as the time to a decrease from baseline of ≥ 10 points with a ≥ 10-point decrease from baseline observed at all subsequent measurements. Reported pain was measured on the Brief Pain Inventory-Short Form.
Key Findings
Median follow-up was 28.0 months (interquartile range [IQR] = 23.9–31.7 months) in the talazoparib/enzalutamide group and 26.8 months (IQR = 23.4–30.6 months) in the placebo/enzalutamide group.
Median time to definitive deterioration in GHS/QOL was 30.8 months (95% confidence interval [CI] = 27.0 months to not estimable) in the talazoparib/enzalutamide group vs 25.0 months (95% CI = 22.9–30.7 months) in the placebo/enzalutamide group (HR = 0.78, 95% CI = 0.62–0.99, P = .038).
Median time to definitive deterioration in urinary symptoms was not estimable (95% CI = not estimable to not estimable) in the talazoparib/enzalutamide group vs 35.9 months (95% CI = 32.3 months to not estimable) in the placebo/enzalutamide group (HR = 0.76, 95% CI = 0.54–1.06, P = .11). No clinically meaningful differences (≥ 10 points) in mean changes from baseline were observed in GHS/QOL or symptom or functional scales between the treatment groups.
No differences were observed between the talazoparib/enzalutamide group and the placebo/enzalutamide group in time to deterioration of pain (HR = 0.98, 95% CI = 0.69–1.40, P = .93) or in mean pain scores (P = .27).
The investigators concluded: “Talazoparib plus enzalutamide prolonged time to definitive deterioration in GHS/QOL vs placebo plus enzalutamide. Together with clinical efficacy and safety data, these results inform the risk−benefit assessment of talazoparib plus enzalutamide in patients with metastatic castration-resistant prostate cancer in TALAPRO-2.”
Nobuaki Matsubara, MD, of the National Cancer Center Hospital East, Chiba, Japan, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Pfizer. For full disclosures of the study authors, visit thelancet.com.
