ASCO 2010-OLAPARIB HAS HIGH RESPONSE RATE FOR OVARIAN CANCER BUT LOW RESPONSE RATE FOR TRIPLE NEGATIVE BREAST CANCER

CHICAGO -- Treatment with the investigational poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib may have some activity against triple-negative breast cancer when combined with paclitaxel, researchers suggested here.

But their enthusiasm for olaparib in this combination is muted by toxicity, particularly neutropenia, they said here at the annual meeting of the American Society of Clinical Oncology.

In the phase 1 study, three of nine women responded to therapy, but four of the women experienced neutropenia. None of these women were given white blood cell growth factor support.

In a second study with 10 women, all of whom were given granulocyte-colony stimulating factor, four achieved a partial response while two women still developed neutropenia.

"The combination of olaparib plus paclitaxel had a generally manageable toxicity profile but was associated with a higher-than-expected incidence of neutropenia, which resulted in a lower paclitaxel (Taxol) dose intensity," said Rebecca Dent, MD, head of breast cancer clinical trials at Sunnybrook and Women's Health Sciences Centre.

"Despite the lower paclitaxel dose intensity, encouraging response rates were seen with this olaparib-plus-paclitaxel regimen," she told MedPage Today at her poster presentation.

In another presentation at the meeting, Karen A. Gelmon, MD, head of the Breast Cancer Tumor Group at the British Columbia Cancer Agency, Vancouver, reported that in a phase II translational study of olaparib, about 41.2% of 64 women with ovarian cancer achieved objective responses when the drug was used as a single agent. She did not observe any responses in 24 patients with triple-negative advanced breast cancer.

Triple negative breast cancer is defined as underexpression of estrogen receptors, progesterone receptors, and HER2-receptors. The women in Dent's study had a mean age of 50 years and had good performance status. They were required to have had at least one prior cytotoxic treatment. Of the 19 women in the study, 14 underwent adjuvant treatment regimens, most of which were taxane-based.

"The level of neutropenia in this study is concerning," said Sumanta Pal, MD, assistant professor of medical oncology and therapeutics research at the City of Hope Comprehensive Cancer Center, Duarte, Calif. "It is a big limitation for this treatment."
Primary source: Journal of Clinical Oncology

Source reference:
Dent R et al, "Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first- or second-line treatment of patients with metastatic triple-negative breast cancer: Results from the safety cohort of a phase I/II multicenter trial" J Clin Oncol 2010; 28: 118s.

Additional source: Journal of Clinical Oncology
Source reference:
Gelmon K et al, "Can we define tumors that will respond PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer" J Clin Oncol 2010; 28: 233s.