Clinical Scorecard: FDA expands talazoparib use in prostate cancer

At a Glance

Key Highlights

• FDA approved talazoparib with enzalutamide for adults with HRR-mutated metastatic androgen pathway modulation-naïve or -sensitive prostate cancer.
• In TALAPRO-3, talazoparib plus enzalutamide reduced the risk of investigator-assessed radiographic progression or death by 52% versus placebo plus enzalutamide (hazard ratio, 0.48).
• Median radiographic progression-free survival was not reached with the combination and was 45.8 months in the control group; overall survival data were immature.
• Grade 3 or higher anemia occurred in 51% with talazoparib plus enzalutamide versus 3% with placebo plus enzalutamide.
• The recommended talazoparib dose is 0.5 mg orally once daily with enzalutamide, alongside androgen deprivation therapy.

Guideline-Based Recommendations

Diagnosis

• Confirm an eligible HRR gene mutation using an FDA-authorized test. FoundationOneCDx and FoundationOne Liquid CDx are identified as approved companion diagnostics.
• In TALAPRO-3, HRR status was determined prospectively using next-generation sequencing of tumor tissue or circulating tumor DNA.

Management

• The recommended talazoparib dose is 0.5 mg orally once daily with enzalutamide until disease progression or unacceptable toxicity.
• Patients must receive a gonadotropin-releasing hormone analog or have undergone bilateral orchiectomy.
• Talazoparib dose reductions are recommended for moderate or severe renal impairment.

Monitoring & Follow-up

• The source states that complete blood counts should be monitored before treatment and monthly thereafter.

Risks

• Grade 3 or higher anemia occurred in 51% of combination-treated patients; anemia led to permanent talazoparib discontinuation in 5%.
• Other commonly reported adverse events included fatigue, decreased neutrophil count, and asthenia.
• Prescribing information warns of myelodysplastic syndrome or acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.

Patient & Prescribing Data

Adults with HRR-mutated metastatic androgen pathway modulation-naïve or -sensitive prostate cancer; eligible mutations must be identified by an FDA-authorized test.

Talazoparib 0.5 mg orally once daily is given with enzalutamide and ongoing androgen deprivation therapy until progression or unacceptable toxicity. Dose reductions are recommended for moderate or severe renal impairment.

Clinical Best Practices

• The source states that eligible patients must have an HRR gene mutation identified by an FDA-authorized test.
• Patients must receive a gonadotropin-releasing hormone analog or have undergone bilateral orchiectomy.
• The source states that complete blood counts should be monitored before treatment and monthly thereafter.
• The source reports anemia and other hematologic risks, including decreased neutrophil count, and lists prescribing-information warnings for myelosuppression.

Related Resources & Content

• FDA
• Pfizer