Breast cancer drugs benefit wider group of patients, trial finds

Newswise – DALLAS – October 28, 2022 – Drug approved to treat breast cancer patients with mutations in the BRCA1 Where BRCA2 genes can also benefit people who have other genetic mutations.

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

“Otherwise, these patients would have very limited treatment options,” said Joshua Gruber, MD, Ph.D., assistant professor of internal medicine at UT Southwestern and member of the Harold C. Simmons Comprehensive Cancer Center. “This study expands the patient population that may benefit from PARP inhibitors.”

Like other PARP inhibitors, talazoparib works by blocking a protein that usually 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, dealing a second fatal blow to the DNA repair machinery.

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

In the new phase 2 trial, Dr. Gruber and his colleagues tested the effectiveness of talazoparib in patients with advanced cancer with less common genetic mutations associated with DNA repair. Previous data suggested that more than 17% of all cancers have such mutations.

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

Among all patients, the average survival time was 5.6 months, and 20% had at least partial tumor shrinkage. As this was a phase 2 trial, there was no control group to compare this data to, but the results were particularly striking for patients with the PALB2 mutations: They survived an average of 6.9 months and all six patients (five with breast cancer, one with pancreatic cancer) showed tumor shrinkage.

The findings underscore the growing importance of genetic testing in guiding treatment for cancer patients, Dr. Gruber said. The team is planning a follow-up trial at UT Southwestern to better understand which patients get the most benefit from talazoparib.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes and includes 24 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 researchers from the Howard Hughes Medical Institute. Full-time faculty of more than 2,900 are responsible for groundbreaking medical advances and committed to rapidly translating scientific research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 inpatients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits annually.

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