Study expands breast cancer patient population that may benefit from PARP inhibitors

Study expands breast cancer patient population that may benefit from PARP inhibitors

A drug approved to treat breast cancer patients with mutations in the BRCA1 or BRCA2 genes may also benefit people with other genetic mutations.

UT Southwestern researchers reported in the journal Nature Cancer that talazoparib successfully shrank the tumors of breast cancer patients with mutations in the PALB2 gene. Patients with this mutation would not have previously qualified for treatment with talazoparib, a cancer drug known as a PARP inhibitor.

These patients would otherwise have very limited treatment options. This study expands the patient population that may benefit from PARP inhibitors.”

Joshua Gruber, M.D., Ph.D., assistant professor of internal medicine at UT Southwestern and member of the Harold C. Simmons Comprehensive Cancer Center

Like other PARP inhibitors, talazoparib works by blocking a protein that normally helps cells repair damaged DNA. Without the ability to repair their DNA, cancer cells accumulate damage and eventually die. In cancers that have other defects in this process - including those with BRCA1/2 mutations - the drug is particularly effective, delivering a deadly second blow to the DNA repair machinery.

In a landmark 2018 study, researchers focused on patients with advanced breast cancer with BRCA mutations — which account for 5% to 10% of all breast cancer cases — and found that talazoparib increased their survival. The Food and Drug Administration approved the drug for this group, and follow-up studies have found that talazoparib also works in prostate and pancreatic cancer patients with BRCA mutations.

In the new phase 2 study, Dr. Gruber and colleagues examined the effectiveness of talazoparib in advanced cancer patients with less common gene mutations related to DNA repair. Previous data suggests that more than 17% of all cancers have such mutations.

Twenty patients were enrolled in the study at Stanford University, where Dr. Gruber previously worked. Thirteen had breast cancer, three had pancreatic cancer, and four had other tumor types. The patients had mutations in eight DNA repair genes. On average, they took one talazoparib pill daily for 23.8 weeks.

For all patients, the average survival time was 5.6 months, and in 20% the tumor had at least partially shrunk. Because this was a phase 2 study, there was no control group with which to compare these data, but the results were particularly notable for patients with PALB2 mutations: They survived an average of 6.9 months, and all six patients (five with breast cancer, one with pancreatic cancer) had tumor shrinkage.

The results underscore the increasing importance of genetic testing in the treatment of cancer patients, said Dr. Gruber. The team is planning a follow-up study at UT Southwestern to better understand which patients benefit most from talazoparib.

Source:

UT Southwestern Medical Center

Reference:

Gruber, JJ, et al. (2022) A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes. Nature cancer. doi.org/10.1038/s43018-022-00439-1.

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