An international consortium of researchers has shown that an
investigational drug, Olaparib, can reduce the size of tumors in women with advanced hereditary ovarian cancer with BRCA gene mutations.
The Phase II ovarian cancer study results - as well as
another Phase II trial in which Cedars-Sinai researchers also participated that
evaluated the drug's effectiveness in the treatment of hereditary breast cancer
- were published in a recent issue of Lancet. The two trials showed similar
levels of response to the genetically-targeted drug in both breast and ovarian
cancers with BRCA mutations.
"These are significant new studies. Olaparib is the first
single-agent, non-chemotherapy treatment to show benefit to patients with
cancers that result from BRCA1 or BRCA2 gene mutations," said William Audeh,
M.D., an oncologist specializing in cancer genetics at Cedars-Sinai's Samuel
Oschin Comprehensive Cancer Institute and first author on the ovarian cancer
study "Until now, treatments for cancer have been selected based upon where in
the body the cancer originated. These two studies suggest that it is the
underlying genetic weakness of a cancer, not the organ of origin, that is the
key to selecting effective therapy."
The first author of the breast cancer study and the
principal investigator for both studies was Andrew Tutt, M.D., Breakthrough
Breast Cancer Research Unit, King's College London School of Medicine.
Olaparib, a Poly ADP ribose polymerase (PARP) inhibitor made
by AstraZeneca, represents a "targeted therapy" approach to cancer treatment -
anticancer drugs that interfere with specific pathways involved in cancer
growth or survival. The PARP enzyme plays a role in DNA repair, including the
repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme appear
to contribute to cancer cell death as well as increase their sensitivity to
Of the 57 patients enrolled in the ovarian cancer study
worldwide, 33 percent of participants showed a significant shrinkage in the
size of their tumors, and in some cases, complete disappearance of their
tumors. Toxicities from the drug were relatively mild, including nausea,
fatigue and anemia.
"Women with advanced BRCA-mutated ovarian cancer have often
been through several chemotherapy regimens, making it difficult to offer
effective treatments," said Audeh. "PARP inhibitors may be a promising new
option for this heavily 'pre-treated' population. "
Ovarian cancer is the fifth leading cause of cancer deaths
among American women, with an estimated 21,550 new cases and 14,600 deaths in
2009. Approximately 10 percent of these cases have an inherited mutation in the
BRCA 1 or 2 genes, the type of cases treated in this trial. Since it is often
difficult to diagnose, many women present with advanced disease, which is
especially challenging to treat.
"These PARP inhibitor studies represent a major change
in the approach to treating cancer that will be reflected in future clinical
trials," said Audeh. "While we studied Olaparib's clinical benefit in patients
known to have specific genetic weaknesses in their cancer cells, it is hoped
that this drug - and others like it - will be an effective tool to treat the
underlying genetic defects found in all types of cancers."