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Adding Veliparib to Chemotherapy

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    Posted: Feb 06 2023 at 12:03pm

Adding veliparib to chemotherapy can extend progression-free survival in patients with “BRCA-like” breast cancer


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

Veliparib belongs to a class of drugs known as PARP inhibitors. PARP inhibitors have been shown to be effective in treating breast cancer with germline mutations in the BRCA1 or BRCA2 gene. But 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.

Results from the trial, which was led by researchers from SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI), are published in Lancet Oncology.

Priyanka Sharma, MD, a SWOG investigator who is professor of medicine at the University of Kansas Medical Center was co-lead author on the paper with Eve Rodler, MD, associate professor of medicine at University of California, Davis.

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. BRCA-like phenotype is noted in 40 to 50 percent of triple negative breast cancers, making these findings and BRCA-like classification relevant for a substantial proportion of patients with TNBC."

Priyanka Sharma, MD, a SWOG investigator

Germline mutations in the BRCA1 or BRCA2 gene increase the number of errors made in the DNA repair process in cells. Poly (ADP-ribose) polymerase – or 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 occurring in the setting of germline BRCA1 or BRCA2 mutations.

Many triple negative tumors, however, 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. The S1416 team asked whether these BRCA-like cancers could also be treated effectively with PARP inhibitors. . . .

. . ."While these results are not immediately practice changing, since veliparib is not FDA approved," Sharma said, "S1416 findings open new clinical trial directions by extending the patient population that could benefit from PARPi therapy. With demonstration of efficacy in BRCA-like phenotype TNBC, S1416 results provide a basis for expanding the therapeutic role of PARP inhibitors (e.g., veliparib) beyond germline BRCA mutation in breast cancer."

https://www.news-medical.net/news/20230131/Adding-veliparib-to-chemotherapy-can-extend-progression-free-survival-in-patients-with-e2809cBRCA-likee2809d-breast-cancer.aspx

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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