PARP Inhibitor Veliparib Might Benefit Women With Resistant Gynecologic Cancers and BRCA Mutation


Key Points

  • Overall, 26% of patients with recurrent or persistent gynecologic cancer with BRCA mutations responded positively to veliparib treatment, including two patients in whom the tumors disappeared completely.
  • Almost half of the patients experienced stable disease for more than 4 months.

Preliminary research suggests that a targeted oral agent may improve outcomes while minimizing side effects in women with gynecologic cancers who carry a BRCA mutation and whose disease is not responding to other therapies. According to a phase II study presented at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer, gynecologic cancer cells that have a BRCA mutation appear to be sensitive to veliparib, an investigational poly(ADP-ribose) polymerase (PARP) inhibitor.

PARP inhibitors prevent cancer cells from repairing themselves after experiencing DNA damage. Research has previously shown that veliparib is effective in combination with chemotherapy, but little data was available to indicate whether veliparib was effective as a single agent. Results of this multicenter trial suggest that it is.

“One criticism of the PARP drugs is they are not active in patients who have developed resistance to other therapies, but we found veliparib appears to be effective in some platinum-resistant patients with recurrent or persistent disease,” said Robert L. Coleman, MD, lead author of the study and Professor and Vice Chair of Clinical Research at The University of Texas MD Anderson Cancer Center, Houston. “Most of these patients have run out of treatment options, and it is very hopeful to potentially have another therapy to offer them.”

Study Details

The study enrolled 52 patients with recurrent or persistent epithelial ovarian, peritoneal, or fallopian tube cancer with germline mutation in BRCA1 or BRCA2 and measurable disease. Fifty patients treated at 1 of 18 centers took veliparib by mouth twice a day with up to two dose reductions for toxicity. The median number of monthly treatment cycles was 6 (ranging from 1 to 22).

Overall, 13 patients (26%) responded positively to the therapy, meaning the tumors shrank in size, including two patients in whom the tumors disappeared completely. In addition, disease was stabilized for more than 4 months in 24 women.

Grade 2 adverse events occurring in > 10% of patients included nausea (46%), fatigue (26%), vomiting (16%), and anemia (14%). Grade 3 adverse events included fatigue in three patients, nausea in two patients, and leukopenia, neutropenia, dehydration, and elevated ALT in one patient each. One patient experienced grade 4 thrombocytopenia. Forty-eight percent of patients had dose reductions.

The investigators concluded that veliparib is active among BRCA-positive women with measurable, recurrent ovarian cancer and demonstrated sufficient clinical efficacy and tolerance to warrant further investigation.

“Patient recruitment can be a problem for many clinical trials; however, this one filled up very quickly, which reflects that women and their doctors understand that PARP inhibitors hold real promise,” said Dr. Coleman.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.