Clinical Trial Shows Benefit of Veliparib in ‘BRCA-Like’ Breast Cancer

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Patients with triple-negative breast cancer treated with veliparib had statistically significantly longer survival than those given placebo.

Results from the SWOG S1416 clinical trial show that adding veliparib to chemotherapy can significantly extend progression-free survival (PFS) in patients with triple-negative breast cancer (TNBC) that has a “BRCA-like” phenotype.

Valiparib is a poly (ADP-ribose) polymerase (PARP) inhibitor, which is a class of medications that have been shown to be effective in treating breast cancer with germline mutations in the BRCA1 or BRCA2 gene. However, this is the first trial to demonstrate a PARP inhibitor benefit in breast cancer that is not BRCA1/2-mutated but is BRCA-like based on the presence of other changes that similarly affect cells’ DNA repair abilities.

“SWOG 1416 is the first trial to report benefit of a PARP inhibitor in metastatic TNBC with a BRCA-like phenotype in absence of germline mutations in BRCA1 or BRCA2 genes,” said co-lead author Priyanka Sharma, MD, in a press release. “BRCA-like phenotype is noted in 40% to 50% of triple negative breast cancers, making these findings and BRCA-like classification relevant for a substantial proportion of patients with TNBC.”

Germline mutations in the BRCA1 or BRCA2 gene increase the number of errors made in the DNA repair process in cells. PARP is an enzyme in cells that helps repair damaged DNA, and drugs that inhibit PARP activity have been shown to be effective in treating breast cancer with germline BRCA1 or BRCA2 mutations.

However, many triple-negative tumors have no germline mutations in these genes but do have other alterations that negatively affect the DNA repair process in ways similar to the effects of germline BRCA1/2 mutations. In the S1416 trial, investigators asked whether these BRCA-like cancers could also be treated effectively with PARP inhibitors.

In the study, 320 patients with metastatic breast cancer were randomized to either cisplatin chemotherapy plus veliparib or cisplatin chemotherapy plus a placebo. Participants had been diagnosed with breast cancer that was either triple-negative or was human epidermal growth factor receptor 2 (HER2)–negative and suspected to be associated to germline mutations in BRCA1/2.

After randomization, the investigators tested patients’ blood and tumor tissue for biomarkers. Based on those results, patients were assigned to 1 of 3 distinct groups based on their type of breast cancer: BRCA-mutated, BRCA-like, or non-BRCA-like.

Among patients who had BRCA-like breast cancer, those treated with veliparib had statistically significantly longer median PFS than those in the placebo arm, with 5.9 months and 4.2 months, respectively. These patients also had a numerically better median overall survival time and objective response rate than patients on the placebo arm, although these differences were not statistically significant.

The investigators also found higher overall rates of grade 3/4 treatment-related adverse events on the veliparib arm than on the placebo arm (74% and 52%, respectively), including higher rates of grade 3/4 neutropenia, anemia, and thrombocytopenia.

“While these results are not immediately practice changing, since veliparib is not FDA approved, S1416 findings open new clinical trial directions by extending the patient population that could benefit from PARP [inhibitor] therapy,” Sharma said in the press release. “With demonstration of efficacy in BRCA-like phenotype TNBA, S1416 results provide a basis for expanding the therapeutic role of PARP inhibitors beyond germline BRCA mutation in breast cancer.”

REFERENCE

S1416 trial results show PARP inhibitor benefit in “BRCA-like” breast cancer. News release. EurekAlert; January 31, 2023. Accessed February 3, 2023. https://www.eurekalert.org/news-releases/978231

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