Posted: Tuesday, June 6, 2023
Combination therapy with the PARP inhibitor talazoparib and the androgen receptor inhibitor enzalutamide may be an effective strategy to improve the rates of progression-free survival in patients with metastatic castration-resistant prostate cancer that harbors homologous recombination repair (HRR) gene alterations, according to an update from Cohorts 1 and 2 of the phase III TALAPRO-2 trial presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5004). The favorable safety profile associated with this combination regimen may help to delay the time to clinically meaningful deterioration in global health status/quality of life, according to Karim Fizazi, MD, PhD, of Institut Gustave Roussy, University of Paris-Saclay, Villejuif, and colleagues.
From 2019 to 2022, a total of 399 patients with metastatic castration-resistant prostate cancer were recruited for the study. All patients had confirmed HRR-deficient disease. Patients were randomly stratified to receive combination treatment with 0.5 mg of talazoparib and 160 mg of enzalutamide (n = 200) or 160 mg of enzalutamide plus a placebo (n = 199).
A significant improvement in radiographic progression–free survival was reported in patients who received the combination treatment (hazard ratio = 0.45). This combination therapy also improved prostate-specific antigen response and the overall relative risk of disease while extending the interval to the need for cytotoxic chemotherapy and antineoplastic therapy. However, patients who received talazoparib plus enzalutamide reported more treatment-related adverse effects (66.2%) compared with those receiving enzalutamide and placebo (37.2%). More grade ≥ 3 hematologic treatment-related adverse events, such as anemia, neutropenia, thrombocytopenia, and leukopenia, were reported with the combination therapy. The burden of these treatment-related adverse events led to the discontinuation of talazoparib in 10.1% of patients and the discontinuation of the placebo in 7.0% of patients.
Disclosure: Full disclosures of the study authors are not available.