Talazoparib plus enzalutamide in high-volume metastatic hormone-naive prostate cancer: a randomized phase 2 trial.

Talazoparib plus enzalutamide achieved a 73% PSA <0.2 ng/ml response rate at 12 months in high-volume metastatic hormone-naive prostate cancer, exceeding efficacy thresholds.

• Why it matters: Understanding whether combining PARP inhibition with androgen receptor blockade offers additional benefits in tumors without HRR gene alterations is crucial for optimizing treatment strategies in this patient group.
• What they did: A randomized phase 2 trial with 54 men compared talazoparib plus enzalutamide to enzalutamide alone, measuring PSA response rates, adverse events, and tumor transcriptional changes.
• The result: While the combination showed clinical activity, it did not demonstrate clear benefit over enzalutamide alone and was associated with higher toxicity, including severe adverse events and therapy-related myeloid neoplasms.