On June 20, 2023, the PARP inhibitor talazoparib was approved for use with enzalutamide in homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer.1
Supporting Efficacy Data
Approval was based on findings in the multicohort, double-blind TALAPRO-2 trial (ClinicalTrials.gov identifier NCT03395197), in which 399 patients with HRR gene–mutated disease were randomly assigned to enzalutamide at 160 mg daily plus daily talazoparib at 0.5 mg (n = 200) or placebo (n = 199). Median radiographic progression–free survival on blinded independent central review was not reached (95% confidence interval [CI] = 21.9 months to not estimable) in the talazoparib group vs 13.8 months (95% CI = 11.0–16.7 months) in the control group (hazard ratio = 0.45, 95% CI = 0.33–0.61, P < .0001). Hazard ratios were 0.20 (95% CI = 0.11–0.36) among 155 patients with BRCA alteration and 0.72 (95% CI = 0.49–1.07) among those without BRCA alteration.
How It Is Used
Patients should concurrently receive a gonadotropin-releasing hormone analog or should have had bilateral orchiectomy. The recommended talazoparib dose is 0.5 mg once daily in combination with enzalutamide until disease progression or unacceptable toxicity; the recommended enzalutamide dose is 160 mg once daily. Product labeling provides instructions for talazoparib dose modification, for adverse reactions and for moderate or severe renal impairment.
Safety Profile
Among 197 vs 199 patients in the TALAPRO-2 safety population of patients with HRR gene–mutated disease, the most common grade 1 to 4 adverse events with an incidence of at least 10% in the talazoparib group and at least 2% vs the control group were fatigue (49% vs 40%), nausea (21% vs 17%), decreased appetite (20% vs 14%), fractures (14% vs 10%), dizziness (13% vs 9%), and dysgeusia (10% vs 4.5%). The most common grade 3 or 4 laboratory abnormalities in the talazoparib group were decreased hemoglobin (41% vs 6%), decreased neutrophils (19% vs 1%), and decreased lymphocytes (13% vs 7%).
OF NOTE
Talazoparib has warnings/precautions for MDS or AML, myelosuppression, and embryofetal toxicity.
Serious adverse events occurred in 30% of the talazoparib group, most commonly anemia (9%) and fracture (3%). Adverse events led to permanent discontinuation of talazoparib in 10% of patients, most commonly anemia (4%) and fatigue, fracture, ischemic heart disease, and spinal cord compression (1% each). Fatal adverse events occurred in 1.5% of patients. Among all 511 patients with metastatic castration-resistant prostate cancer treated with talazoparib plus enzalutamide in TALAPRO-2, 39% required blood transfusion. Two patients were diagnosed with myelodysplastic syndrome or acute myeloid leukemia (MDS or AML).
Talazoparib has warnings/precautions for MDS or AML, myelosuppression, and embryofetal toxicity.
REFERENCE
1. Talzenna (talazoparib) capsules, for oral use, prescribing information, Pfizer, Inc, June 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211651s010lbl.pdf. Accessed July 10, 2023.
