An oral tablet form of a poly-ADP ribose polymerase (PARP) inhibitor, olaparib, given in combination with chemotherapy, was safe in heavily pretreated patients with ovarian cancer, and patients with BRCA mutations may have a better response compared with those without a BRCA mutation, according to phase Ib clinical trial data presented at the Marsha Rivkin Center for Ovarian Cancer Research-AACR 10th Biennial Ovarian Cancer Research Symposium, held earlier this month in Seattle.1
Tablets, Not Capsules, Used in Study
“This study is one of the first studies to use olaparib tablets instead of olaparib capsules,” said Saul Rivkin, MD, Founder and Chairman of the Marsha Rivkin Center for Ovarian Cancer Research, and a Research Scientist at the Swedish Cancer Institute, both in Seattle. “The goal was to find the maximum tolerated dose of olaparib tablets plus weekly metronomic carboplatin and paclitaxel in patients with relapsed ovarian cancer.
“This treatment regimen provided a response rate of 66% in heavily pretreated ovarian cancer patients,” said Dr. Rivkin.
Dr. Rivkin and colleagues enrolled 14 heavily pretreated ovarian cancer patients (from three to eight prior therapies), ages 42 to 77. Patients received paclitaxel and carboplatin weekly for 3 out of 4 weeks, with increasing doses of olaparib. The maximum tolerated dose of olaparib was found to be 150 mg twice daily for 3 consecutive days of each week of each cycle.
Of the 12 evaluable patients, four had a complete response (33%), four had a partial response (33%), two had stable disease (16%), and two had disease progression (16%).
BRCA mutations were detected in the tumors of three patients with a complete response, three with a partial response, one with stable disease, and one with disease progression .
The most common grade 3 toxicities included neutropenia, leukopenia, lymphopenia, and anemia. There was no evidence of gastrointestinal, renal, cardiac, hepatic, pulmonary, or dermatologic toxicities in any of the patients with a toxicity grade greater than 2.
The investigators plan to recruit up to 40 additional patients in the phase II extension of this protocol. ■
Disclosure: This study was funded by the Dulien Fund and AstraZeneca. Dr. Rivkin reported no potential conflicts of interest.
1. Rivkin S: Phase Ib/II with expansion of patients at the MTD study of olaparib plus weekly (metronomic) carboplatin and paclitaxel in relapsed ovarian cancer. Marsha Rivkin Center for Ovarian Cancer Research-AACR 10th Biennial Ovarian Cancer Research Symposium. Presented September 9, 2014.