In phase 1 and 2 clinical trials, olaparib, a small-molecule poly(ADPribose) polymerase (PARP) inhibitor, has demonstrated objective responses in women with breast or ovarian cancer and BRCA1 and BRCA2 mutations. Results of a new study show that olaparib may be a promising therapy for women with aggressive ovarian cancer (Gelmon KA, et al. Lancet Oncol. 2011;12:852-861).
In an open-label, nonrandomized phase 2 clinical study conducted in 6 centers in Canada, a total of 91 women (aged ≥18 years) with advanced highgrade serous and/or undifferentiated ovarian carcinoma (N = 65) or triplenegative breast cancer (N = 26) were enrolled and stratified according to BRCA mutation or lack of mutation; all of the patients received oral olaparib 400 mg twice daily. The primary end point was the objective complete or partial response rate, based on the Response Evaluation Criteria in Solid Tumors.
Objective responses were not reported for patients with breast cancer; of the 63 patients with ovarian cancer who were evaluable, objective responses were confirmed in 7 (41%) of the 17 women with BRCA mutations and in 11 (24%) of the 46 patients without a mutation.
A total of 13 (20%) patients with ovarian cancer discontinued the study early for different reasons, including worsening disease, adverse events, and voluntary discontinuation. At study end, 13 patients with ovarian cancer and 26 of those with breast cancer were still receiving olaparib.
The most common adverse events reported in both groups were fatigue, nausea, vomiting, and decreased appetite. Drug-related adverse events were reported in 88% of patients with ovarian cancer.
