FDA approves PARP inhibitor talazoparib for BCRA-positive, HER2‑negative advanced breast cancer

The US Food and Drug Administration (FDA) approved talazoparib (Talzenna, Pfizer Inc.) for patients with advanced BCRA-positive, HER2‑negative locally advanced or metastatic breast cancer. Talazoparib is administered orally and belongs to the class of drugs called poly (ADP-ribose) polymerase (PARP) inhibitors, which block the enzymes involved in repairing of damaged DNA.

BRCA mutation is responsible for 25-30% of all hereditary breast cancers and 5-10% of all breast cancers. The FDA has also approved the BRACAnalysis CDx test (Myriad Genetic Laboratories, Inc.) to identify patients with breast cancer with deleterious or suspected deleterious germline BRCA mutation who are eligible for talazoparib.

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 the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA.

The approval is based on results of international EMBRACA (NCT01945775) trial, an open-labeled, RCT involving 431 patients with gBRCAm HER2‑negative locally advanced or metastatic breast cancer. The other inclusion criteria were having received prior treatment with an anthracycline and/or a taxane (unless contraindicated) in the neoadjuvant, adjuvant, and/or metastatic treatment setting. Patients were excluded if they have received more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease.

The patients were randomized to receive 1 mg oral talazoparib or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS), as assessed by a blinded independent central review.

At the median follow-up of 11.2 months, talazoparib reduced the risk of disease progression or death by 46% versus chemotherapy. Patients in talazoparib arm demonstrating median survival of 8.6 months as opposed to 5.6 months in the chemotherapy arm.

Patients on talazoparib also showed higher objective response rate (ORR) as compared to patients on other chemotherapy drugs (62.6% vs. 27.2%; odds ratio, 4.99; 95% CI, 2.9-8.8; 2-sided P value <.0001). The FDA defines ORR as the “proportion of patients with a tumor size reduction of a predefined amount and for a minimum period of time,” and ORR is one of the many oncology endpoints for the approval of cancer drugs and biologics.

Most commonly reported side effects of the drug include nausea, headache, fatigue, anemia, neutropenia, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite. The drug also comes with a warning and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.

BRACAnalysis CDx also has a diagnostic indication for the detection of deleterious or suspected deleterious mutations in BRCA1 and BRCA2 genes for patients with ovarian cancer to select therapy for olaparib (Lynparza) and/or rucaparib (Rubraca).

FDA approval

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