Approved by : FDA, EMA, NCCN
Approval Time : Oct. 16, 2018
Direct Target : PARP1,PARP2
Drug Type : Single-target inhibitor
Alteration : Deleterious Mutations
Indications : The poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib was approved to be used for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.
Mechanism Of Action :
Talazoparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2, which play a role in DNA repair. In vitro studies with cancer cell lines that harbored defects in DNA repair genes, including BRCA 1 and BRCA 2, have shown that talazoparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, decreased cell proliferation, and apoptosis. Talazoparib anti-tumor activity was observed in human patient-derived xenograft breast cancer tumor models bearing mutated BRCA 1 or mutated BRCA 2 or wild-type BRCA 1 and BRCA 2.
Dosage : The recommended dose of talazoparib in the current indication is 1 mg taken orally once daily, with treatment continued until disease progression or unacceptable toxicity. Recommended dose reductions for adverse events are stepwise to 0.75, 0.5, and 0.25 mg daily. Treatment should be discontinued if more than three dose reductions are required. The recommended starting dose in patients with moderate renal impairment is 0.75 mg once daily. Talazoparib has not been studied in patients with severe renal impairment or patients requiring hemodialysis.
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