What are the benefits of Talazoparib (a poly (ADP-ribose) polymerase inhibitor) in the treatment of prostate cancer?

From the Guidelines

Talazoparib, in combination with enzalutamide, is a highly effective treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) who have mutations in DNA damage repair genes, as evidenced by the significant improvement in radiographic progression-free survival in the TALAPRO-2 trial 1.

Key Benefits of Talazoparib

• The medication offers a significant benefit for certain prostate cancer patients, particularly those with mCRPC who have mutations in DNA damage repair genes like BRCA1, BRCA2, ATM, and others.
• Talazoparib, typically dosed at 1 mg once daily, works as a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to cancer cell death.
• In the TALAPRO-2 trial, talazoparib combined with enzalutamide significantly improved radiographic progression-free survival compared to enzalutamide alone, with a hazard ratio of 0.63 (95% CI, 0.51-0.78; P<.0001) 1.

Important Considerations

• The most common side effects of talazoparib include anemia, fatigue, nausea, and decreased platelet counts, so regular blood monitoring is necessary during treatment.
• Patients should continue treatment until disease progression or unacceptable toxicity occurs.
• Talazoparib is most effective in patients who have undergone genetic testing confirming the presence of DNA repair mutations, making genetic testing an important step before starting this therapy.

Targeted Therapy Option

• The medication represents an important targeted therapy option that exploits specific genetic vulnerabilities in prostate cancer cells, offering a more personalized approach to treatment.
• Based on the results of the TALAPRO-2 trial, the FDA approved talazoparib plus enzalutamide for HRRm mCRPC in June 2023, with a category 1 recommendation for those without prior docetaxel or prior novel hormone therapy, and a category 2A recommendation for those with prior therapy 1.

From the FDA Drug Label

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for: HRR Gene-mutated mCRPC • In combination with enzalutamide for the treatment of adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC). (1.2) The benefits of Talazoparib in the treatment of prostate cancer are:

• Treatment of HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC) in combination with enzalutamide 2 Key points:
• Indicated for use in combination with enzalutamide
• Specific patient population: HRR gene-mutated mCRPC

From the Research

Benefits of Talazoparib in Prostate Cancer Treatment

• Talazoparib has shown antitumor activity in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations 3, 4, 5, 6, 7
• The treatment has demonstrated a manageable safety profile, with common adverse events including anemia, nausea, decreased appetite, and asthenia 3, 6
• Talazoparib has been associated with improved health-related quality of life (HRQoL) and reduced pain burden in patients with mCRPC and DDR/HRR alterations 5
• The combination of talazoparib with enzalutamide has shown favorable results across multiple efficacy endpoints, although it is associated with increased rates of hematological adverse events 4
• Talazoparib's mechanism of action, chemical properties, pharmacokinetics, and pharmacodynamics make it a promising treatment for mCRPC and potentially for metastatic hormone-sensitive prostate cancer (mHSPC) 7

Efficacy of Talazoparib

• The objective response rate was 29.8% in patients with mCRPC and DDR-HRR alterations treated with talazoparib 3
• Talazoparib showed durable antitumor activity in men with advanced mCRPC and DDR-HRR gene alterations who had been heavily pretreated 3, 6
• The treatment was ranked as the most efficacious treatment across multiple efficacy outcomes, except for overall survival, in a network meta-analysis 4

Safety Profile of Talazoparib

• The most common grade 3-4 treatment-emergent adverse events were anemia, thrombocytopenia, and neutropenia 3, 6
• Talazoparib was associated with a manageable safety profile, with common adverse events generally being grades 1 and 2 6
• The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days 6