Agent active in PCa patients with BRCA mutations

In what is being called the largest clinical trial to examine the efficacy of poly(ADP-ribose) polymerases (PARP) inhibitor therapy in BRCA 1/2 carriers with diseases other than breast and ovarian cancer, the oral drug olaparib was found to be effective against advanced forms of both prostate and pancreatic cancer.

Results of the study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia and Sheba Medical Center in Tel Hashomer, Israel, were presented during the American Society of Clinical Oncology’s annual meeting in Chicago earlier this week. BRCA made headlines last month when actress Angelina Jolie revealed that she’d had a preventive double mastectomy after testing positive for BRCA1.

The multicenter research team, including investigators from across the United States, Europe, Australia, and Israel, studied nearly 300 patients with inherited BRCA1 and BRCA2 mutations who had advanced cancers that were still growing despite standard treatments. Study participants, comprised of patients with prostate, breast, ovarian, pancreatic, 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 senior author Susan Domchek, MD, of the University of Pennsylvania’s Abramson Cancer Center. “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.”

Four of eight prostate cancer patients (50%) responded to the therapy, as measured by objective clinical criteria. The therapy also appeared to halt disease progression even in those whose tumors did not shrink: two (25%) of the prostate patients had stable disease at 8 weeks after beginning olaparib. Overall survival at 1 year was 50% for the prostate cancer patients.

The most commonly reported side effects of olaparib were mild to moderate fatigue and nausea (each experienced by 59% of patients) and transient episodes of vomiting (37%). Seventeen percent of patients experienced anemia, and 4% of patients suffered side effects that led to discontinuation of therapy.

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

Dr. Domchek has received research funding from Abbott Laboratories and AstraZeneca.

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