Opening Doors for Precision Medicine in Breast Cancer

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Veliparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with chemotherapy demonstrated positive results for patients with BRCA-like phenotype triple-negative breast cancer with no new side effects observed, according to study results.

PARP inhibitors are approved by the Food and Drug Administration and primarily used as a single agent to treat breast cancer with a BRCA1 or BRCA2 (BRCA1/2) mutation — such cases account for only 5% to 7% of patients with breast cancer. However, data are lacking on whether PARP inhibitors are effective in combination with chemotherapy to treat BRCA-like phenotype breast cancer, which accounts for 40% to 50% of triple-negative breast cancer cases. BRCA-like phenotype breast cancer have been shown to be homologous deficient (when the cancer cell is unable to repair breaks in the DNA), which could lead to sensitivity to PARP inhibitors.

In this study, published in The Lancet Oncology journal, researchers evaluated the efficacy of cisplatin chemotherapy in combination with veliparib or placebo in three groups of patients with breast cancer: those with BRCA1/2 (37 patients), BRCA-like (101 patients) and non-BRCA mutations (109 patients).

At a median follow-up of 11.1 months, progression-free survival (time during and after treatment when the patient lives without disease) was 6.2 months with veliparib and 6.4 months with placebo in the BRCA1/2 mutated group. In the BRCA-like group, progression-free survival was higher with veliparib plus cisplatin at 5.9 months compared to 4.2 months with placebo plus cisplatin. In the non-BRCA group there was no improvement in progression free survival with addition of veliparib to cisplatin chemotherapy

Dr. Priyanka Sharma, lead author on the study and breast medical oncologist at the University of Kansas Medical Center in Kansas City, Kansas, noted that this is the first study, to her knowledge, that demonstrated PARP inhibitors’ effectiveness beyond a BRCA1/2 mutation in breast cancer.

“(The results) are certainly positive,” she said in an interview with CURE®. “This really opens doors for larger studies to investigate this approach of a PARP inhibitor combined with chemotherapy in patients with BRCA-like phenotype triple-negative breast cancer.” It is known that patients with metastatic triple negative breast cancer have poor prognosis, Sharma continued, with an average survival of under two years. So, exploring newer treatment options, such as PARP inhibitors, is important for this patient population. “We definitely need better treatment options for these patients, and this could be one of them, if this activity can be confirmed in larger studies,” she added. “This really is moving us a little bit closer to precision medicine as we look to expand the therapeutic role of PARP inhibitors in breast cancers beyond the BRCA mutation.”

The most common severe or worse side effects included neutropenia (low white blood cell count; 46% in the veliparib group versus 20% in the placebo group), leukopenia (a condition where the body doesn’t have enough disease-fighting leukocytes in the blood; 27% vs. 7%), anemia (23% vs. 8%) and thrombocytopenia (low blood platelet count; 19% vs. 3%). Serious side effects from treatment occurred in 31% of patients on veliparib and 36% of patients on placebo.

The addition of a PARP inhibitor to chemotherapy had more toxicity compared to chemotherapy. However, Sharma and researchers expected this finding as the combination has demonstrated more side effects compared to chemotherapy alone in other tumor types. No new side effects were reported and those that were, were manageable with dose reeducations and delays.

“Future trials could study intermittent schedule of PARP inhibitor or in other words treatment schedule with built in treatment breaks and this can potentially help reduce the side effects toxicity management,” she concluded. “But I think the bottom line is there were no new toxicity signals noted.”

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