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Gynecologic Cancers: PARP Inhibitor May Benefit Women with BRCA Mutation

DiGiulio, Sarah

doi: 10.1097/01.COT.0000450369.01186.ef


The PARP inhibitor veliparib may improve outcomes for women with the BRCA1 or BRCA2 mutation with recurrent epithelial ovarian cancers that are resistant to other therapies, according to Phase II clinical trial data reported at the Society of Gynecologic Oncology Annual Meeting on Women's Cancer (Abstract 136).

The oral cancer drug inhibits the enzymes PARP-1 and PARP-2 (which are responsible for single-strand DNA damage). Previous research has found the drug to be effective in combination with chemotherapy, but the new findings suggest that it is also effective as a single-agent.

“We found that veliparib appears to be effective in some platinum-resistant patients with recurrent or persistent disease,” Robert L. Coleman, MD, the study's lead author and Professor and Vice Chair of Clinical Research at the University of Texas MD Anderson Cancer Center, said in a news release. “Most of these patients have run out of treatment options, and it is very hopeful to potentially have another therapy to offer them.”

The study followed 50 women with recurrent or persistent epithelial ovarian, peritoneal, or fallopian tube cancer who carried a germline mutation in BRCA1 or BRCA2 and had had up to three prior cytotoxic regimens. The women received 400 milligrams of veliparib twice daily, for cycles of 28 days. The median number of cycles administered was six (treatment was continued to progression, toxicity, or voluntary withdrawal).

Thirteen patients responded to the therapy (26%)—two patients having achieved a complete response (all measureable and non-measurable disease having resolved on therapy) and 11 having achieved a partial response. Disease was stabilized for more than four months in 24 women (48%).

Median progression-free survival was eight months, and median overall survival was nearly 19.7 months. According to data updated since the meeting, the six-month, event-free rate was 60 percent.

In terms of adverse events, there was one case of grade 4 thrombocytopenia; other non-hematological adverse events were more common, but of low grade. Grade three events reported were fatigue, nausea, leukopenia, neutropenia, dehydration, and alanine aminotransferase; grade two events were nausea, fatigue, vomiting, and anemia; and adverse events were the most common reason for dose delay and dose reduction (with approximately half the study cohort experiencing dose reduction due to a non-hematological toxicity).

The anticipated response rate was lowered because the trial allowed resistant, as well as sensitive patients with BRCA-positive disease, Coleman noted via email. But, even among the platinum-resistant patients (whom are often considered to be PARP-resistant), there was “chemo-like” or better response—suggesting that these patients may still respond to this class of agent, he said.



“A large number of patients developed stable disease. Since most ovarian cancer patients will not be cured by therapy for recurrent disease, managing it with low toxicity agents, particularly oral agents, is a ‘win.’”

© 2014 by Lippincott Williams & Wilkins, Inc.
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