Early findings suggest this cancer drug may be effective against advanced tumors caused by genetic mutations

Researchers at Sparrow Health System, part of University of Michigan Health, hope results from a recent study on a breast and prostate cancer drug for patients with all types of advanced cancers can eventually lead to a decline in cancer-related deaths, especially for those with specific gene mutations.

Results of the phase 2 Targeted Agent and Profiling Utilization Registry, known as TAPUR, study were presented at the American Society of Clinical Oncology conference.

The findings are based on responses from 28 patients with 16 different types of tumors, including lung, breast, prostate, pancreas, and melanoma.

They suggest the FDA-approved drug talazoparib may be effective in any cancer that has a BRCA1/2 mutation, which results in uncontrollable cell growth. Talazoparib inhibits PARP, a protein that helps damaged cells repair themselves. As a cancer treatment, PARP inhibitors stop the protein enzymes from doing repair work in cancer cells, which causes the cells to die.

The researchers say the results with talazopairb exceeded their expectations.

“Nobody expected such a high response rate because these patients have advanced disease, and they were heavily pretreated and had exhausted all the other standard-of-care treatment options,” said Gordan Srkalovic, M.D., Ph.D., the medical director of the Sparrow Herbert-Herman Cancer Center.

More on the study

Srkalovic and his colleagues expected the cancer would shrink or stabilize in 15% of patients or less.

Instead, they reported that the drug was effective in 57%of the patients, with 36%showing shrinkage of their tumor.

One patient with non-melanoma skin cancer showed no evidence of cancer after using the drug, nine patients saw a partial response, and the cancer neither decreased nor increased in six patients for at least 16 weeks.

The median time a patient in the cohort lived during and after the treatment was 24 weeks, and the median overall survival was 71 weeks. Researchers found that 22 patients had significant side effects from the drug, with three patients discontinuing talazoparib because of serious adverse events.

However, Srkalovic says the toxicity profile was as expected and didn’t raise any red flags.

Currently, oncologists tailor treatment to the individual patient’s specific tumor. However, physicians are now looking more into treating patients based on the mutations in their cells, rather than where the tumor is found inside the body.

Women with BRCA1/2 genes have up to a 75% risk of developing breast cancer and up to a 50%risk of developing ovarian cancer during their lifetime.

While risks in male carriers are not as high as female BRCA mutation carriers, they still face an increased potential of breast and pancreatic cancer, as well as an elevated risk of aggressive prostate cancer.

“This result opens an avenue for the treatment of cancers other than breast and ovarian,” Srkalovic said.

Srkalovic notes that other TAPUR cohort studies have also exceeded expectations.

He and other colleagues found that temsirolimus, which inhibits the mTOR mutation, had activity that stopped the growth of tumors in a cohort of 29 patients with various advanced solid tumors harboring mTOR. 

The PARP inhibitor olaparib was also reported to have blocked the growth of cancer cells in a TAPUR cohort of 30 patients with metastatic castrate-resistant prostate cancer and BRCA1/2 mutations.

In 2021, another TAPUR study, led by University of Michigan Health Rogel Cancer Center, researchers found that pembrolizumab - a type of immunotherapy known as a checkpoint inhibitor - can provide clinical benefit to some patients with metastatic breast cancer whose tumors were found to have a high number of mutations, and whose cancer continued to progress with standard treatments.

By blocking the binding of a protein called PD-1, pembrolizumab releases the brakes on the patient's immune response, enabling the patient's body to better attack the cancer.

"Immunotherapy doesn't work for every patient, but when it does work, it can have really profound effects," said lead author Ajjai Alva, MBBS, an oncologist at Michigan Medicine and principal investigator for the TAPUR trial site at U-M.

"When it comes to a biomarker to tell us which patients will respond best to immunotherapy, we still haven't found the perfect marker, the holy grail — but we have found a very good candidate biomarker in high tumor mutational burden."

Alva notes that the TAPUR study is part of a larger movement toward individualized medicine through the use of next generation sequencing and the molecular nuances it uncovers in each patient's tumor.

"There's growing evidence that next-generation sequencing should be considered part of the standard of care for all patients with advanced cancers," he said.

In addition to Srkalovic, the talazoparib study’s authors colleagues from other institutions Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Eugene R Ahn, Gregory Brouse, John K Chan, Inderjit Mehmi, Maya Khalil, Herbert Leon Duvivier, Anu G. Gaba, Harshraj Leuva, Ramya Thota, Kathleen J Yost, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky.

Paper cited: “Talazoparib (Tala) in patients (pts) with solid tumors with BRCA1/2 mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study,” J Clin Oncol. DOI: 10.1200/JCO.2023.41.16_suppl.311