Hereditary breast cancers resulting from BRCA gene mutations are often aggressive and what’s known as triple-negative, meaning they don’t produce any of the three main proteins targeted by drugs commonly used to fight breast cancer.
Now a City of Hope study indicates that a powerful combination of drugs might benefit women with this type of cancer who haven’t responded to other therapies.
A phase I trial assessed the effectiveness of a platinum-based drug combined with veliparib, a PARP inhibitor drug. The drug combination rated an impressive 64 percent clinical benefit rate, meaning that 64 percent of the patients had tumor shrinkage or their disease did not progress while on the treatment.
PARP1 is a protein that cancer cells need to replicate and is important for repairing single-strand breaks in DNA. PARP inhibitors target this protein and cause double-strand breaks in the DNA of cancer cells, leading these cells to die. The drug is given orally, and does not cause many of the common side effects of chemotherapy, such as hair loss or nausea.
The platinum-based drug, carboplantin, is used to treat other cancers, including ovarian and lung cancer, but not used as often for breast cancer.
Phase I trials, designed to test safety, often don’t give good indication of the potential clinical benefit of a treatment, but the results seen in this early trial are promising, said Jeffrey Weitzel, M.D., director of the Division of Clinical Cancer Genetics at City of Hope.
Along with George Somlo, M.D., professor, Departments of Medical Oncology and Therapeutics Research and Hematology & Hematopoietic Cell Transplantation, who presented the results in a poster discussion session at the American Society of Clinical Oncology’s annual meeting in Chicago, Weitzel is leading the phase II portion of this national multicenter trial testing the combination therapy.
“Some of the women in the study had already been through as many as five rounds of chemotherapy without any response,” Weitzel said. “These results are encouraging.”
Of the 28 women enrolled in the study, 14 percent had a complete response -- meaning that their cancers were no longer detectable. Another 43% showed a partial tumor response, and for an additional 7 percent of the women, the therapy did not shrink their cancer but seemed to stop progression. So all together, 64% of the participants benefited.
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number 1R21CA137684. The content is solely the responsibility of the authors and does not necessarily represent that official views of the National Institutes of Health.
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