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ASCO 2013: PARP Inhibitor Shows Activity in Pancreatic, Prostate Cancers among Patients Carrying BRCA Mutations

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Key Points

  • Olaparib was found to be effective against advanced pancreatic and prostate cancers. Five of 23 patients with pancreatic cancer (22%) and four of eight patients with prostate cancer (50%) responded to the therapy.
  • An additional eight (35%) of the patients with pancreatic cancer had stable disease at 8 weeks after beginning olaparib, as did two (25%) of the patients with prostate cancer.
  • Overall survival at 1 year was 41% for the patients with pancreatic cancer and 50% for the patients with prostate cancer.

In the largest clinical trial to date to examine the efficacy of PARP inhibitor therapy in BRCA1/2 carriers with diseases other than breast and ovarian cancer, the oral drug olaparib was found to be effective against advanced pancreatic and prostate cancers. Results of the study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania and Sheba Medical Center in Tel Hashomer, Israel, were presented at the 2013 ASCO Annual Meeting (Abstract 11024).

BRCA1/2 Genes Are ‘Achilles Heel’ in Novel Approach

The multicenter research team, which included 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 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,” says the study’s senior author, Susan Domchek, MD, Director of the Basser Research Center for BRCA in 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.”

Five of 23 patients with pancreatic cancer (22%) and four of eight patients with prostate cancer (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 patients with pancreatic cancer studied had stable disease at 8 weeks after beginning olaparib, as did two (25%) of the patients with prostate cancer. Overall survival at 1 year was 41% for the patients with pancreatic cancer and 50% for the patients with prostate cancer.

Breast and Ovarian Cancer Activity Confirmed

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 1 year. Among 62 patients with metastatic breast cancer 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%). 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.

‘New Paradigm in Cancer Therapy’

“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,” Dr. Domchek said. “PARP inhibitors such as olaparib represent the most promising new treatment for individuals suffering from cancer based on inherited BRCA1 and BRCA2 gene mutations.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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