Expanding the Use of PARP Inhibitors in Breast Cancer: Focus on Talazoparib and PALB2

By: Kayci Reyer
Posted: Wednesday, February 1, 2023

According to phase II trial research presented in Nature Cancer, the PARP inhibitor talazoparib may be an effective treatment option for more patients with advanced breast cancer, and also perhaps for those with other tumors. Previously shown to benefit patients with BRCA1 or BRCA2 mutations, talazoparib also appears to demonstrate antitumor activity in patients with PALB2 mutations as well.

“These patients would otherwise have very limited treatment options,” noted Joshua J. Gruber, MD, PhD, of The University of Texas (UT) Southwestern Medical Center, Dallas, in a UT Southwestern press release. “This study expands the patient population that can benefit from PARP inhibitors.”

Between August 2015 and December 2018, the phase II trial enrolled 20 patients with HER2-negative breast cancer (n = 13), pancreatic cancer (n = 3), or other solid tumors (n = 4), all of whom had mutations across eight homologous recombination pathway genes not including BRCA1 or BRCA2. Patients received 1 mg of talazoparib daily for at least one cycle, with all patients discontinuing treatment by April 2019.

The median time on therapy was 23.8 weeks. Median progression-free survival, longest for patients with a germline PALB2 mutation at 6.9 months, was 5.5 months overall, 5.6 months for patients with breast cancer, and 2.6 months for patients with other cancers. Among patients with breast cancer, the overall response and clinical benefit rates were 31% and 54%, respectively. No responses were recorded among patients with other cancers; the clinical benefit rate for that cohort was 29%.

Treatment-related adverse events were manageable and in line with the treatment’s safety profile. Nonhematologic adverse events occurred in 70% of patients, and 55% of patients experienced hematologic adverse events.

Disclosure: For full disclosures of the study authors, visit nature.com.

Nature Cancer