The FDA ( Food and Drug Administration ) has approved Talzenna ( Talazoparib ), a poly (ADP-ribose) polymerase ( PARP ) inhibitor, for patients with deleterious or suspected deleterious germline BRCA-mutated ( gBRCAm ), HER2‑negative locally advanced or metastatic breast cancer.
Patients must be selected for therapy based on an FDA-approved companion diagnostic for Talazoparib.
Approval was based on EMBRACA, an open‑label trial randomizing 431 patients ( 2:1 ) with gBRCAm HER2‑negative locally advanced or metastatic breast cancer to receive Talazoparib ( 1 mg ) or physician’s choice of chemotherapy ( Capecitabine, Eribulin, Gemcitabine, or Vinorelbine ).
All patients were required to have a known deleterious or suspected deleterious gBRCA mutation and must have received no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease.
Patients were required to have received treatment with an anthracycline and/or a taxane ( unless contraindicated ) in the neoadjuvant, adjuvant, and/or metastatic treatment setting.
The primary efficacy outcome was progression-free survival ( PFS ) according to RECIST 1.1, as assessed by blinded independent central review.
Estimated median progression-free survival was 8.6 and 5.6 months in the Talazoparib and chemotherapy arms, respectively ( hazard ratio, HR=0.54; 95% CI: 0.41, 0.71; p less than 0.0001 ).
The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.
Most common ( greater than or equal to 20% ) adverse reactions of any grade were fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, decreased appetite.
FDA has also approved the BRACAnalysis CDx test to identify patients with breast cancer with deleterious or suspected deleterious gBRCAm who are eligible for Talazoparib.
The effectiveness of the BRACAnalysis CDx test was based on the EMBRACA trial population for whom deleterious or suspected deleterious gBRCAm status was confirmed with either prospective or retrospective testing with BRACAnalysis CDx.
The recommended Talazoparib dose is 1 mg taken as a single oral daily dose, with or without food. ( Xagena )
Source: FDA, 2018