Instructions for Talazoparib

1. Generic name: Talazopanib

Product name:Talzenna

All names: talazoparib, Talazoparib, talazoparib tosylate capsules, talazoparib tosylate, talazoparib, Dasheng cancer

2. Indications:

BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer: Talazoparib is indicated as a single agent for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer.

2. Metastatic castration-resistant prostate cancer (mCRPC) with HRR gene mutations: Talazopanib is used in combination with enzalutamide to treat adult patients with metastatic castration-resistant prostate cancer with homologous recombination repair (HRR) gene mutations.

3. Usage and dosage:

1. Before medication: Before patients take medication, doctors will choose to use talazopanib based on the presence of germline BRCA mutations and HRR gene mutations.

2. Recommended dosage:

(1) BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer: The recommended dose of talazopanib is 1 mg orally once daily until disease progression or unacceptable toxicity occurs

（2) Metastatic castration-resistant prostate cancer (mCRPC) with HRR gene mutations: The recommended dose of talazopanib is 0.5 mg orally once daily in combination with enzalutamide until disease progression or unacceptable toxicity occurs. Patients receiving combination therapy should also receive concomitant GnRH analog therapy or should undergo bilateral orchiectomy.

3. Dose adjustment: In order to control adverse reactions, consider interrupting treatment and reducing or not reducing the dose according to the severity and clinical manifestations. If more than three dose reductions are required, talazopanib therapy should be discontinued.

(1) Breast cancer: The first dose of talazopanib is reduced to 0.75 mg once daily, the second dose is reduced to 0.5 mg once daily, and the third dose is reduced to 0.25 mg once daily.

(2) Prostate cancer: The first dose of talazopanib is reduced to 0.35 mg once daily, the second dose is reduced to 0.25 mg once daily, and the third dose is reduced to 0.1 mg once daily.

4. Kidney function damage:

(1) Moderate renal impairment (CLcr30-59mL/min): The recommended dose of talazopanib for patients with breast cancer is 0.75 mg orally once daily; for patients with prostate cancer, the recommended dose is 0.35 mg orally once daily.

(2) Severe renal impairment (CLcr15-29mL/min): The recommended dose of talazopanib for patients with breast cancer is 0.5 mg orally once daily; for patients with prostate cancer, the recommended dose is 0.25 mg orally once daily.

5. Drug interactions: Avoid coadministration of talazopanib with glycoprotein (P-gp) inhibitors. If it cannot be avoided, reduce its oral dose to 0.75 mg once daily. When the P-gp inhibitor is discontinued, increase the dose of talazopanib (after 3-5 half-lives of the P-gp inhibitor) to the dose before starting the P-gp inhibitor; the dose also needs to be modified according to the occurrence of adverse reactions.

4. Adverse reactions:

In clinical studies for the treatment ofBRCA-mutated HER2-negative locally advanced or metastatic breast cancer, the most common (≥20%) adverse reactions (including laboratory abnormalities) included decreased hemoglobin, neutropenia, lymphopenia, thrombocytopenia, fatigue, increased glucose, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase, decreased calcium, nausea, headache, vomiting, alopecia, diarrhea, and decreased appetite.

In clinical studies of combination therapyThe most common (≥10%) adverse reactions (including laboratory abnormalities) in metastatic castration-resistant prostate cancer with HRR gene mutations include decreased hemoglobin, neutropenia, lymphopenia, fatigue, thrombocytopenia, decreased calcium, nausea, decreased appetite, decreased sodium, decreased phosphate, fracture, decreased magnesium, dizziness, increased bilirubin, decreased potassium, and dysgeusia.

5. Storage:

Talazopanib Store20°C to 25°C (68°F to 77°F); excursions allowed between 15°C and 30°C (59°F to 86°F).

6. Special groups:

1. Females: Due to the potential for serious adverse reactions in breastfed children from talazopanib, lactating women are advised not to breastfeed during treatment with talazopanib and for 1 month after the last dose; females of reproductive potential are advised to use effective contraception during treatment and for 7 months after the last dose.

2. Men: Based on genotoxicity and animal reproduction studies, it may impair fertility in males of reproductive potential. It is recommended that male patients and pregnant partners of female partners of reproductive potential use effective contraception during treatment with talazopanib and for 4 months after the last dose.

7. Mechanism of action:

Talazopanib is an inhibitor of poly(ADP-ribose) polymerase (PARP), including PARP1 and PARP2, which play a role in DNA repair. In vitro studies in cancer cell lines defective in DNA repair genes, including BRCA1 and BRCA2, suggest that talazopanib-induced cytotoxicity may involve inhibition of PARP enzyme activity and increased formation of PARP-DNA complexes, resulting in DNA damage, reduced cell proliferation, and apoptosis. Talazoparib antitumor activity was observed in patient-derived xenograft breast cancer models harboring mutated BRCA1 or mutated BRCA2 or wild-type BRCA1 and BRCA2.

The original drug of talazopanib has not yet been marketed in China, so it has not been included in medical insurance. The original drug specification of talazopanib listed overseas is 0.25mg*30 capsules, and the price per box may be around RMB 10,000 (the price may fluctuate due to exchange rate effects), which is relatively expensive. There are also cheaper generics of talazopanib overseas. For example, the price of a box of 1mg*30 pills produced by a Laos pharmaceutical factory may be more than 3,000 yuan (the price may fluctuate due to the exchange rate).