Talazoparib

DAE Class; Rx

Common Brand Names; Talzenna

• Antineoplastics, PARP Inhibitors

PARP inhibitor
Used for BRCA-mutated HER2-negative locally advanced or metastatic breast cancer and HRR-mutated metastatic castration-resistant prostate cancer
Monitor complete blood counts; an interruption of therapy or dose reduction may be necessary for myelosuppression

Indicated for adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer

Indicated in combination with enzalutamide for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC)

None

Adverse effects include all grades unless otherwise stated

>10%

Decreased hemoglobin (90%)

Decreased leukocytes (84%)

Decreased lymphocytes (76%)

Decreased neutrophils (68%)

Fatigue (62%)

Decreased platelets (55%)

Increased glucose (54%)

Anemia (53%)

Nausea (49%)

Increased AST (37%)

Increased alkaline phosphatase (36%)

Neutropenia (35%)

Increased ALT (33%)

Headache (33%)

Decreased calcium (28%)

Thrombocytopenia (27%)

Vomiting (25%)

Alopecia (25%)

Diarrhea (22%)

Decreased appetite (21%)

Abdominal pain (19%)

Dizziness (17%)

Leukopenia (17%)

Grade 3

• Decreased hemoglobin (39%)
• Anemia (38%)
• Neutropenia (18%)
• Decreased neutrophils (17%)
• Decreased lymphocytes (17%)
• Decreased leukocytes (14%)
• Thrombocytopenia (11%)
• Decreased platelets (11%)

1-10%

Dysgeusia (10%)

Dyspepsia (10%)

Stomatitis (8%)

Lymphopenia (7%)

Grade 3

• Decreased platelets (4%)
• Decreased neutrophils (3%)
• Fatigue (3%)
• Increased glucose (2%)
• Increased alkaline phosphate (2%)
• Vomiting (2%)
• Headache (2%)
• Increased AST/ALT (1-2%)
• Decreased calcium (1%)

Grade 4

• Thrombocytopenia (4%)
• Neutropenia (3%)
• Anemia (1%)

<1%

Decreased appetite, Grade 3

Nausea, Grade 3

Decreased lymphocytes, Grade 4

Decreased leukocytes, Grade 4

Based on its mechanism of action and findings from animal data, fetal harm may occur when administered to a pregnant woman (see Pregnancy)

Myelosuppression

• Myelosuppression (eg, anemia, leukopenia/neutropenia, and/or thrombocytopenia) reported; monitor blood counts monthly during treatment
• If hematological toxicities do not resolve within 28 days, discontinue therapy and refer patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics

Myelodysplastic syndrome/acute myeloid leukemia

• Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) reported; MDS/AML reported (0.3%) in solid tumor in clinical studies; duration of treatment in these patients prior to developing MDS/AML was 4 months and 24 months, respectively
• Do not start until patients have adequately recovered from hematological toxicity caused by previous chemotherapy; Monitor blood counts monthly during treatment
• For prolonged hematological toxicities, interrupt and monitor blood cell counts weekly until recovery; if levels do not recover within 4 weeks, refer patient to a hematologist for further investigations
• If MDS/AML is confirmed, discontinue treatment

Drug interactions overview

• P-gp and BCRP transporters substrate

• Effect of P-gp inhibitors

  • Coadministration with P-gp inhibitors may increase talazoparib exposure
  • In clinical studies, coadministration with P-gp inhibitors (ie, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil) resulted in an ~45% increase in talazoparib exposure and an increase in the rate of talazoparib dose reduction
  • When coadministering with P-gp inhibitors not listed above, monitor for potential increased adverse reactions

• Effect of BCRP inhibitors

  • Coadministration with BCRP inhibitors may increase talazoparib exposure
  • If coadministration cannot be avoided, monitor potential increased adverse reactions when coadministering

Pregnancy

Based on findings from animal studies and its mechanism of action, embryofetal harm may occur when administered to pregnant females

No data available on use in pregnant females to inform a drug-associated risk

Lactation

There are no data on the presence of talazoparib in human milk, its effects on milk production, or on breastfed children

Advise lactating women not to breastfeed during treatment and for ≥1 month after the final dose

Adults

Breast cancer: 1 mg/day PO.
Prostate cancer: 0.5 mg/day PO.

Geriatric

Breast cancer: 1 mg/day PO.
Prostate cancer: 0.5 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established

Talazoparib