Olaparib Tablet Found Safe and Effective in Heavily Pretreated Patients With Ovarian Cancer
A phase Ib clinical trial of the tablet form of olaparib, a PARP inhibitor, in combination with paclitaxel and carboplatin chemotherapy in heavily pretreated patients with advanced-stage ovarian cancer finds the drug to be safe and effective, especially in those women with BRCA gene mutations. The study by Rivkin et al was presented at the Marsha Rivkin Center for Ovarian Cancer Research–AACR 10th Biennial Ovarian Cancer Research Symposium, held September 8 to 9, in Seattle.
Study Methodology
The purpose of this study was to establish the maximum-tolerated dose of olaparib and to evaluate dose-limiting toxicities and response to therapy of the tablet form of olaparib plus carboplatin and paclitaxel in women with stage III or IV ovarian cancer. The researchers enrolled 14 heavily pretreated (from three to eight prior therapies) patients in the study, aged 42 to 77. All the patients were tested for BRCA2 and BRCA2 gene mutations.
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.
Study Findings
Of the 12 evaluable patients in the study, 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.
There were no grade 4 toxicities. The most common grade 3 toxicities included neutropenia, leucopenia, lymphopenia, anemia, fatigue, and myelodysplastic syndrome. There was no evidence of gastrointestinal, cardiac, hepatic, pulmonary, or dermatologic toxicities in any of the patients.
The investigators plan to recruit up to 40 additional patients in a phase II extension of this protocol.
“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,” said Saul Rivkin, MD, Founder and Chairman of the Marsha Rivkin Center for Ovarian Cancer Research in Seattle, and lead author of the study, in a statement. “Medical researchers are discovering and investigating new and innovative therapies for the treatment of ovarian cancer. We are consistently working toward improving the quality of life and survival for all ovarian cancer patients.”
The study was funded by the Dullen Fund and AstraZeneca. Dr. Rivkin reported no conflicts of interest.
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®.
