Talazoparib (Talzenna®, Pfizer Inc.), an orally available poly (ADP-ribose) polymerase (PARP) inhibitor, has been approved by the United States Food and Drug Administration (FDA) for the treatment of patients with HER2-negative locally advanced or metastatic breast cancer with known or suspected deleterious germline BRCA (gBRCA) mutations. Eligibility for talazoparib therapy must be determined using the BRACAnalysis CDx® test (Myriad Genetic Laboratories Inc.), which the FDA has also approved as a companion diagnostic.
Approval of talazoparib was based on outcomes of the EMBRACA trial, which involved patients with HER2-negative locally advanced or metastatic breast cancer and a known or suspected deleterious gBRCA mutation. Trial participants had received prior treatment with an anthracycline and/or a taxane, unless contraindicated, in the neoadjuvant, adjuvant, and/or metastatic treatment setting. They had received no more than three cytotoxic chemotherapy regimens for locally advanced or metastatic disease.
In EMBRACA, 431 patients were randomized to receive the recommended dose of talazoparib—1 mg taken orally as a single daily dose—or physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). Talazoparib produced a median progression-free survival of 8.6 months, compared with 5.6 months for chemotherapy. Talazoparib also outperformed chemotherapy by producing greater overall improvements and delayed time to definitive clinically meaningful deterioration in multiple cancer-related and breast cancer-specific symptoms.
"Patients with germline BRCA-positive breast cancer are typically diagnosed at a younger age than those with nonhereditary breast cancer, and there are no therapies specifically approved for them outside of current standard-of-care therapies," commented lead investigator Jennifer Litton, MD, Associate Professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center. "EMBRACA supports the potential of talazoparib to give these patients additional time without disease progression, compared to chemotherapy."
Approval of the BRACAnalysis CDx test to identify talazoparib-eligible patients was also based on the EMBRACA trial population, for whom the test was used either prospectively or retrospectively to confirm deleterious gBRCA mutation status.
"Myriad's BRACAnalysis CDx test was shown in the EMBRACA trial to accurately identify certain patients with a germline BRCA-mutation who may benefit from [talazoparib]," stated 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."
Talazoparib's most common adverse reactions of any grade, affecting at least 20% of patients, included fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite. The prescribing information lists warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.
For More Information
Clinicaltrials.gov (2018). A study evaluating talazoparib (BMN 673), a PARP inhibitor, in advanced and/or metastatic breast cancer patients with BRCA mutation (EMBRACA Study) (EMBRACA). NLM Identifier: NCT01945775.
Ettl J, Quek RGW, Lee KH, et al (2018). Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol, 29(9):1939-1947. DOI:10.1093/annonc/mdy257
Litton JK, Rugo HS, Ettl J, et al (2018). Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med, 379(8):753-763. DOI:10.1056/NEJMoa1802905