Tuesday, September 9, 2014

PARP inhibitor effective against ovarian cancer with BRCA mutation

NOTE:  I am posting this because basal-like TNBC is similar to ovarian cancer on the molecular level and some experts say that treatment for ovarian cancer might be effective for this form of TNBC.

 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.

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.

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