Talazoparib Receives FDA Approval in BRCA-Mutated, HER2-Negative Breast Cancer

Talazoparib has been approved by the FDA for treatment of patients with deleterious or suspected deleterious germline <em>BRCA</em>-mutated, HER2-negative locally advanced or metastatic breast cancer, according to Pfizer, the manufacturer of the PARP inhibitor.

Talazoparib (Talzenna) has been approved by the FDA for the treatment of patients with deleterious or suspected deleterious germlineBRCA-mutated, HER2-negative locally advanced or metastatic breast cancers, according to Pfizer, the manufacturer of the PARP inhibitor.

The FDA has also approved the BRACAnalysis CDx test. Developed by Myriad Genetic Laboratories, Inc., this test is used to identify deleterious or suspected deleterious germlineBRCA-mutated disease in patients with breast cancer who are eligible for talazoparib. Patients must be selected for To receive talazoparib, patients must be selected by this FDA-approved companion diagnostic.

“We congratulate Pfizer on obtaining FDA approval of TALZENNA for certain patients living with metastatic breast cancer, and we are excited to expand the use of BRACAnalysis CDx as the companion diagnostic test,” said Lloyd Sanders, president of Myriad Oncology. “We estimate there are more than 60,000 patients diagnosed with or who progress to metastatic breast cancer in the United States every year who qualify for a BRACAnalysis CDx test.”

The decision is based on findings from the international, open-label EMBRACA trial, in which talazoparib reduced the risk of disease progression or death by 46% versus chemotherapy in patients withBRCA-positive advanced breast cancer. In the study, 431 patients with germlineBRCA-mutated, HER2-negative locally advanced or metastatic breast cancer were randomized to receive 1 mg of talazoparib or physician’s choice of chemotherapy, which included capecitabine, eribulin, gemcitabine, or vinorelbine.

To be eligible for enrollment, all patients were required to have received no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease. Moreover, patients must have received treatment with an anthracycline and/or a taxane, unless contraindicated, in the neoadjuvant, adjuvant, and/or metastatic setting. The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review.

Results demonstrated that, at a median follow-up of 11.2 months, the median PFS was 8.6 months (95% CI, 7.2-9.3) in the talazoparib arm and 5.6 months (95% CI, 4.2-6.7) in the chemotherapy arms, respectively (HR, 0.54; 95% CI: 0.41-0.71;P<.0001). The objective response rate (ORR) was 62.6% (95% CI, 55.8-69.0) versus 27.2% (95% CI, 19.3-36.3), respectively (odds ratio, 4.99; 95% CI, 2.9-8.8; 2-sidedPvalue <.0001).

The indication for talazoparib includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity. The most common all-grade adverse events associated with fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite.

The efficacy of BRACAnalysis CDx was based on the EMBRACA trial patient population for whom deleterious or suspected deleterious germlineBRCA-mutated status was confirmed with either prospective or retrospective testing with BRACAnalysis CDx.

BRACAnalysis CDx is defined as an in vitro diagnostic device created for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of theBRCA1andBRCA2genes using genomic DNA obtained from whole blood specimens collected in EDTA. Moreover, single nucleotide variants and small insertions and deletions are identified by polymerase chain reaction (PCR) and Sanger sequencing, while large deletions and duplications inBRCA1andBRCA2are detected using multiplex PCR.

BRACAnalysis CDx also has a diagnostic indication for the detection of deleterious or suspected deleterious mutations inBRCA1andBRCA2genes for patients with ovarian cancer to select therapy for olaparib (Lynparza) and/or rucaparib (Rubraca).

“Myriad’s BRACAnalysis CDx test was shown in the EMBRACA trial to accurately identify certain patients with a germlineBRCA-mutation who may benefit from TALZENNA,” said Johnathan Lancaster, MD, PhD, chief medical officer of Myriad Genetics. “It is important for patients to know their BRACAnalysis CDx results so they can fully understand their treatment options.”


Litton JK, Rugo HS, Ettl J, et al. A phase 3 trial comparing talazoparib, an oral PARP inhibitor, to physician&rsquo;s choice of therapy in patients with advanced breast cancer and a germlineBRCA-mutation. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS6-07.