SEATTLE -- An oral tablet form of a PARP inhibitor, olaparib, given in combination with chemotherapy, was safe in heavily pretreated ovarian cancer patients, 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 Sept. 8-9.
"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 percent 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 (from three to eight prior therapies), ages 42 to 77. Patients received paclitaxel and carboplatin weekly, three weeks out of four, with increasing doses of olaparib. The maximum tolerated dose of olaparib was found to be 150 mg twice daily for three consecutive days of each week of each cycle.
Of the 12 evaluable patients, four had a complete response (33 percent), four had a partial response (33 percent), two had stable disease (16 percent), and two had disease progression (16 percent).
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.
This study was funded by the Dulien Fund and AstraZeneca. Rivkin declares no conflicts of interest.
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 35,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in 97 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with over 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.