Olaparib Tablet Safe in Relapsed Ovarian Cancer Patients

In June 2014, the FDA's Oncologic Drugs Advisory Committee voted against offering accelerated approval of olaparib, a poly ADP ribose polymerase (PARP) inhibitor, for maintenance treatment of platinum-sensitive relapsed ovarian cancer with germline BRCA mutation that completely or partially responded to platinum-based chemotherapy. Instead, the agency recommended waiting until the results of the phase III trial are available in 2015 before the committee made a decision.

However, the results of an investigational study evaluating the tablet form of olaparib have recently been presented and, although in very early stages, seem promising. In this new study, the oral tablet form of olaparib, given in combination with chemotherapy, was found to be safe and effective in treating advanced relapsed ovarian cancer patients, especially those with BRCA mutations. This phase Ib clinical trial data was presented last month at the Marsha Rivkin Center for Ovarian Cancer Research–American Association for Cancer Research 10th Biennial Ovarian Cancer Research Symposium.

The purpose of this research was to determine the maximum tolerated dose of olaparib tablets and to evaluate dose-limiting toxicities and response to a combination therapy of carboplatin/paclitaxal and olaparib. According to researcher Saul Rivkin, MD, founder and chairman of the Marsha Rivkin Center for Ovarian Cancer Research, and a research scientist at the Swedish Cancer Institute, this was one of the first studies using olaparib tablets as opposed to the capsule form. The tablets pack a higher dosage in a smaller package than the hard-to-swallow olaparib capsules.

“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 said.

A study from 2013 led by researchers at The Institute of Cancer Research in London and The Royal Marsden NHS Foundation Trust also found that olaparib and chemotherapy can, together, be effective in helping women with BRCA-mutated ovarian cancer live longer than they would if treated with chemotherapy alone.

Rivkin and colleagues enrolled 14 heavily pretreated ovarian cancer patients (from three to eight prior therapies). The patients, aged between 42 and 77 years, 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, four had a partial response, two had stable disease, and two had disease progression.

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 side effects of the combination treatment included neutropenia, leukopenia, lymphopenia, and anemia. There was no evidence of GI, cardiac, hepatic, pulmonary, or dermatologic toxicities in any of the patients.

"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 investigators plan to recruit up to 40 additional patients in the phase II extension of this protocol.