The FDA’s approvals were based on results from the ongoing EMBRACA Phase 3 trial (NCT01945775), which evaluated the safety and effectiveness of 1 mg of Talzenna — compared to physician’s choice of chemotherapy including capecitibine, eribulin, gemcitabine, or vinorelbine — in patients with inherited BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.
The study enrolled 431 patients who previously had been treated with an anthracycline (like doxorubicin) and/or a taxane (such as such as paclitaxel and docetaxel) and no more than three previous chemotherapy regimens for locally advanced or metastatic cancer.
The trial met its primary goal, with Talzenna-treated patients living significantly longer without their disease progressing (8.6 months) than those given standard chemotherapy (5.6 months). These results highlighted a 46% reduction in the risk of cancer progression or death with Talzenna use.
This benefit was consistent across several patient subgroups, including women with triple-negative (a tumor not producing estrogen, progesterone, or HER2 receptors) or hormone receptor-positive breast cancer, patients with a history of brain metastases, and patients previously treated or untreated with chemotherapy.
Talzenna was also found to significantly delay clinically meaningful deterioration in patients’ global health or quality of life, compared with chemotherapy.
The most commonly reported adverse reactions were anemia, fatigue, nausea, low levels of neutrophils (a type of white blood cell), headache, low platelet levels, hair loss, vomiting, diarrhea, and decreased appetite.
The prescribing information for Talzenna includes warnings and precautions for blood-associated conditions and cancers, and embryo-fetal toxicity.
The effectiveness of the companion diagnostic test was confirmed by the accurate identification of enrolled patients with BRCA mutations with either prospective or retrospective testing.
“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 Talzenna,” Johnathan Lancaster, MD, PhD, Myriad Genetics’ chief medical officer, said in a press release. “It is important for patients to know their BRACAnalysis CDx results so they can fully understand their treatment options.”
“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,” said Lloyd Sanders, company president.
EMBRACA is the largest study to date examining a PARP inhibitor in patients with advanced or metastatic breast cancer and inherited BRCA mutations.
PARP inhibitors, such as Talzenna, suppress the function of the PARP enzyme, which acts to repair DNA damage in cells.
In patients with BRCA mutations, the PARP enzyme is particularly important in repairing DNA damage. When this enzyme is prevented from doing its job, cells — particularly fast-growing cancer cells — can accumulate enough DNA damage to kill them.
Talzenna has a dual mechanism of action, both in suppressing PARP function and also in trapping the enzyme at the site of DNA damage, preventing it from being used in further DNA repair attempts.
The European Medicines Agency (EMA) is currently reviewing Talzenna’s application to treat patients with metastatic breast cancer with inherited BRCA mutations.