PARP inhibitor applications for advanced pancreatic and prostate cancer

Oral olaparib has been found effective against advanced pancreatic and prostate cancers with BRCA 1/2 mutations. In the largest clinical trial of its kind to date, researchers examined the efficacy of PARP inhibitor therapy in BRCA 1/2 carriers with diseases other than breast and ovarian cancer. Their results will be presented at the annual meeting of the American Society of Clinical Oncology in early June in Chicago, Illinois.

This study enrolled nearly 300 patients with inherited BRCA1 and BRCA2 mutations who had advanced cancers that were still growing despite standard treatments. The study participants had breast, ovarian, pancreatic, prostate, and other cancers. All took olaparib.

"Our results show that the BRCA1 or BRCA2 genes inherited by some patients can actually be the Achilles heel in a novel, personalized approach to treat any type of cancer the patient has," said the study's senior author, Susan Domchek, MD, of the Basser Research Center for BRCA at the University of Pennsylvania School of Medicine. "As many as 3% of patients with pancreatic and prostate cancer have an inherited mutation in BRCA1 or BRCA2. Our findings have implications for many patients beyond those with breast and ovarian cancer."

Five of 23 pancreatic cancer patients (22%) and four of eight prostate cancer patients (50%) responded to the therapy, as measured by objective clinical criteria. Importantly, the therapy also appeared to halt disease progression even in those whose tumors did not shrink: an additional eight (35%) of the pancreatic cancer patients studied had stable disease at 8 weeks after beginning olaparib, as did two (25%) of the prostate patients. Overall survival at one year was 41% for the pancreatic cancer patients, and 50% for the prostate cancer patients.

For patients with breast and ovarian cancer, the study confirmed the previously reported activity of olaparib, although tumors treated in this study were much more advanced than in prior studies. For example, in 193 patients with ovarian cancer in whom cisplatin was no longer effective for controlling advanced disease, 31% had partial or complete tumor regression on olaparib, and 64% were alive at one year. Among 62 patients with metastatic breast cancer patients who had already received at least three chemotherapy regimens, 13% responded to new therapy and 45% of patients were alive at 1 year.

The authors found that treatment with olaparib is very well-tolerated. The most commonly reported side effects were mild to moderate fatigue and nausea (each experienced by 59% of patients), and transient episodes of vomiting (37%). Anemia was experienced by 17% of patients, and 4% of patients suffered side effects that led to discontinuation of therapy.

As of January 2013, 33 patients remained on the study.

"This study underscores a new paradigm in cancer therapy. We can better fashion treatments for our patients based on a personalized assessment of the genetic factors underlying the cancer," Domchek said.
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