Adding talazoparib to first-line treatment with enzalutamide improves radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to research presented at the 2023 ASCO Genitourinary Cancers Symposium.
Talazoparib reduced the risk of progression or death by 37% in this phase 3 trial, according to study presenter Neeraj Agarwal, MD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City.
The trial, TALAPRO-2 (ClinicalTrials.gov Identifier: NCT03395197), enrolled 805 patients with previously untreated mCRPC. The patients were randomly assigned to receive talazoparib at 0.5 mg daily and enzalutamide at 160 mg daily (n=402) or placebo plus enzalutamide at 160 mg daily (n=403).
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Baseline characteristics were similar between the arms. The median age was 71 years in both arms (overall range, 36-91 years). Most patients had bone metastasis (86.8% in the talazoparib arm and 84.9% in the placebo arm), and a minority were HRR-deficient (21.1% and 20.8%, respectively).
The primary endpoint was rPFS. The median follow-up for rPFS was 24.9 months in the talazoparib arm and 24.6 months in the placebo arm.
The median rPFS was not reached in the talazoparib arm and was 21.9 months in the placebo arm (hazard ratio [HR], 0.63; 95% CI, 0.51-0.78; P <.001). The rPFS was significantly better with talazoparib across all subgroups except among patients with metastasis only in soft tissues (P =.07).
Talazoparib improved rPFS in HRR-deficient patients (HR, 0.46; 95% CI, 0.30-0.70; P <.001) and in patients who were not HRR deficient or had unknown HRR status (HR, 0.70; 95% CI, 0.54-0.89; P =.004).
Talazoparib was also associated with a prolonged time to prostate-specific antigen progression (HR, 0.72; 95% CI, 0.58-0.89; P =.002), cytotoxic chemotherapy (HR, 0.49; 95% CI, 0.38-0.65; P <.001), and second PFS (HR, 0.77; 95% CI, 0.61-0.98; P =.04).
In the interim overall survival analysis (31% mature), there was no significant difference between the treatment arms (HR, 0.89; 95% CI, 0.69-1.14; P =.35).
The rate of treatment-related adverse events (AEs) was 89.7% in the talazoparib arm and 69.6% in the placebo arm. The most common AEs leading to dose reductions of talazoparib were anemia (43.2%), neutropenia (15.1%), and thrombocytopenia (5.5%). There were no treatment-related deaths in the talazoparib arm, but there were 2 in the placebo arm.
“To conclude, talazoparib plus enzalutamide resulted in a statistically significant and clinically meaningful improvement in rPFS … over placebo plus enzalutamide across the all-comer population and prespecified subgroups in the first-line mCRPC setting,” Dr Agarwal said. “Results from the primary analysis of the TALAPRO-2 trial support the use of talazoparib plus enzalutamide as a first-line treatment in men with mCRPC, regardless of HRR gene alteration status.”
Disclosures: This research was supported by Pfizer and Astellas. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Agarwal N, Azad A, Carles J, et al. TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). ASCO GU 2023. February 16-18, 2023. Abstract LBA17.
This article originally appeared on Cancer Therapy Advisor
