An oral tablet form of a 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. This data was presented at the Marsha Rivkin Center for Ovarian Cancer Research–AACR 10th Biennial Ovarian Cancer Research Symposium, in Seattle, Washington.
“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, Washington. “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. It was surprisingly tolerable with no grade 4 toxicities,” said Rivkin.
“The outlook for ovarian cancer patients with advanced disease is not equivalent to that of breast cancer, and a lot of work needs to be done to improve the cure rate,” Rivkin added. “Medical researchers are discovering and investigating new and innovative therapies for the treatment of ovarian cancer. We are constantly working toward improving the quality of life and survival for all ovarian cancer patients.”
Rivkin and colleagues enrolled 14 heavily pretreated ovarian cancer patients, who had had from three to eight prior therapies, and who were age 42 to 77 years. Patients received paclitaxel and carboplatin weekly, in 3 of every 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%).
Three patients with a complete response, three with a partial response, one with stable disease, and one with disease progression had BRCA mutations detected in their tumors.
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.