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Veliparib safe, effective among women with BRCA-mutated gynecologic cancers
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The PARP inhibitor veliparib demonstrated activity with acceptable toxicity among women with recurrent or persistent epithelial, ovarian, peritoneal or fallopian tube cancer who harbored BRCA1 or BRCA2 mutations, according to results of a phase 2 study presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in Tampa, Fla.
“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,” Robert L. Coleman, MD, professor and vice chair of clinical research at The University of Texas MD Anderson Cancer Center, said in a press release.
Robert L. Coleman
Coleman and colleagues evaluated data from 50 patients (median age, 57 years) with BRCA1 or BRCA2 mutations from 18 centers. Fourteen women had received one prior non-PARP therapy, 18 had received two prior therapies and 18 had received three. Thirty women had platinum-resistant disease and 20 were platinum sensitive.
Patients received twice-daily veliparib (ABT-888, AbbVie) in 400-mg doses in 28-day cycles for a median of 5.5 cycles (range, 1-16).
Overall, the rate of confirmed response was 26% (90% CI, 16-38), which included one complete response and 12 partial responses. Researchers found a higher percentage of patients who were platinum sensitive responded than those who were platinum resistant (35% vs. 20%).
Median PFS in the entire cohort was 8.11 months (90% CI, 5.45-8.77), and 44% of patients were event-free at 6 months. OS data were not available at the time of the analysis. Eighteen patients had not progressed, and five patients with stable disease were still receiving the study drug.
Disease progression was the most common reason for treatment discontinuation (46%). Twenty-four patients (48%) received dose reductions due to toxicity.
The most common adverse events were grade 2 nausea (46%), fatigue (26%) vomiting (16%) and anemia (14%). Three patients experienced grade 3 fatigue and two patients experienced grade 3 nausea. One patient each experienced grade 3 leukopenia, neutropenia, dehydration and elevated alanine aminotransferase levels, and researchers reported one case of grade 4 thrombocytopenia.
“Most of these patients run out of treatment options, and it is very hopeful to potentially have another therapy to offer them,” Coleman said. “Patient recruitment can be a problem for many clinical trials; however, this one filled up quickly, which reflects that women and their doctors understand that PARP inhibitors hold real promise.”
For more information:
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Coleman RL. Abstract #136. Presented at: Society of Gynecologic Oncology Annual Meeting; March 22-24, 2014; Tampa, Fla.
Perspective
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Maurie Markman, MD
In this report, Coleman and colleagues describe the experience of the Gynecologic Oncology Group with the administration of a novel PARP inhibitor, veliparib, in platinum-resistant ovarian cancer. The objective response rate of 20% in this specific setting is of interest, as it approximates the biological activity of other active single agents in platinum-resistant ovarian cancer, including single-agent pegylated liposomal doxorubicin, bevacizumab (Avastin, Genentech) and weekly paclitaxel.
As previous studies have revealed the impressive clinical activity of another PARP inhibitor, olaparib (AZD-2281, AstraZeneca), in a randomized phase 2 trial when employed as a maintenance strategy following a second-line response to platinum-based therapy in ovarian cancer, it will be interesting to determine if veliparib might be even more beneficial based on its potential utility in the setting of platinum resistance.
However, the current report does suggest a note of caution. As veliparib is an oral agent, the 46% and 16% incidence of grade ≥2 nausea and vomiting, respectively, is a potential serious concern. Future research efforts should be directed at more effective control of this side effect of treatment, or perhaps altering the dose and/or schedule to prevent or minimize its occurrence.
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