Dr Vidula on the Evaluation of Talazoparib in BRCA1/2-Mutated Metastatic Breast Cancer

Neelima Vidula, MD, breast medical oncologist, Mass General Cancer Center, assistant professor of Medicine, Harvard Medical School, discusses an ongoing phase 2 study (NCT03990896) evaluating the highly potent PARP inhibitor talazoparib (Talzenna) in patients with somatic BRCA1/2-mutated metastatic breast cancer.

This investigator-initiated clinical trial is evaluating the treatment of patients with metastatic breast cancerwho harbor a somatic BRCA1/2 mutation in the absence of a known germline BRCA1/2 mutation. The trial is including patients with triple-negative breast cancer or hormone receptor (HR)–positive/HER2-negative disease, Vidula expands. The rationale for conducting this study is based on previously published data that demonstrated that cell free DNA and tumor tissue genotyping identified high rates of actionable mutations in patients with metastatic breast cancer, leading to selection for genotype-direct therapy, including a portion who have somatic BRCA1/2 mutations, Vidula adds.

Vidula notes that a portion of these detectable mutations are pathogenic, meaning that they are likely to respond to a PARP inhibitor. Therefore, investigators developed a circulating tumor cell culture from a patient who had a pathogenic somatic BRCA1/2 mutation. In preclinical testing, investigators demonstrated that a PARP inhibitor led to growth inhibition in this culture, she continues.

PARP inhibitors currently have a role in the treatment of patients with HER2-negative advanced breast cancer who have germline BRCA1/2 mutations, she says. However, this only accounts for approximately 5% of patients, Vidula says. Eliciting responses in patients with somatic BRCA1/2 mutations could potentially expand the role for PARP inhibitors to a larger subset of patients with advanced breast cancer, Vidula concludes.