The European Commission has approved Talzenna ( Talazoparib ), an oral poly (ADP-ribose) polymerase ( PARP ) inhibitor, as monotherapy for the treatment of adult patients with germline breast cancer susceptibility gene ( gBRCA ) 1/2-mutations, who have human epidermal growth factor receptor 2-negative ( HER2- ) locally advanced ( LA ) or metastatic breast cancer ( MBC ).
Patients should have been previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments.
Patients with hormone receptor-positive ( HR+ ) breast cancer should have been treated with a prior endocrine-based therapy, or be considered unsuitable for endocrine-based therapy.
The European Commission’s approval of Talzenna is based on results from the EMBRACA trial - the largest phase 3 study of a PARP inhibitor in gBRCA-mutated, HER2- LA or MBC.
The global trial evaluated once-daily Talazoparib compared to physician’s choice standard chemotherapy ( Capecitabine, Eribulin, Gemcitabine or Vinorelbine ) in patients with an inherited BRCA1/2 mutation in triple-negative or HR+/HER2- LA or MBC who may have received up to three prior cytotoxic chemotherapy regimens for their advanced disease.
The primary endpoint was progression-free survival ( PFS ), as assessed by blinded independent central review ( BICR ).
In the EMBRACA trial, Talazoparib has significantly outperformed chemotherapy, extending median PFS to 8.6 months compared to 5.6 months for those treated with standard chemotherapy [ 95% CI: 7.2-9.3 vs. 4.2-6.7, respectively ].
The superior PFS benefit with Talazoparib was observed across prespecified patient populations, including patients with triple-negative breast cancer, HR+/HER2- disease, with or without a history of CNS metastasis, and those who received prior cytotoxic chemotherapy regimens.
Secondary endpoints from the EMBRACA trial included objective response rate ( ORR ), overall survival ( OS ) and safety.
Talazoparib has demonstrated an ORR of 62.6% ( 95% CI: 55.8-69.0 ), more than double that in the standard chemotherapy arm ( 27.2% ) ( 95% CI: 19.3-36.3 ).
Overall survival ( OS ) is an event-driven endpoint and the data are not yet mature.
Based on pooled data from patients who received 1 mg Talazoparib in clinical studies for solid tumors, the most common adverse reactions ( greater than or equal to 25% ) of patients receiving Talazoparib were fatigue ( 57.1% ), anemia ( 49.6% ), nausea ( 44.3% ), neutropenia ( 30.2% ), thrombocytopenia ( 29.6% ) and headache ( 26.5% ).
Grade 3 or higher adverse reactions ( greater than or equal to 10% ) in patients treated with Talazoparib were anemia ( 35.2% ), neutropenia ( 17.4% ) and thrombocytopenia ( 16.8% ).
BRCA1 and BRCA2 are human genes that produce proteins involved in DNA repair. When either of these genes is altered or mutated, DNA repair may not progress correctly. This can lead to the development of certain types of cancer such as breast cancer.4BRCA mutations can be hereditary ( germline ) or occur spontaneously ( somatic ).
Together, germline BRCA1 and BRCA2 mutations account for about 25 to 30% of hereditary breast cancers and approximately 3 to 6% of all breast cancers.
Epidemiologic studies have indicated that individuals with gBRCA-mutated breast cancer are diagnosed in their 30s-40s, which is approximately 20 years younger than the overall breast cancer population.
BRCA-mutated breast cancer is metastatic if the disease has spread beyond the breast or to other parts of the body, including the bones, liver, lung or brain.
There is currently no cure for MBC, the most advanced stage ( stage IV ) of the disease. The goal of treatment is to delay or slow disease progression while maintaining quality of life.
Current European and U.S. clinical guidelines recommend gBRCA testing to inform therapeutic considerations for HER2- LA or MBC patients. ( Xagena )
Source: Pfizer, 2019