Ovarian and Breast Cancer Drug, Olaparib, is Effective in a Significant Number of Men with Advanced Prostate Cancer.

A major trial has concluded that a pioneering drug from AstraZeneca, olaparib, developed to treat women with inherited cancers, can also benefit men with certain types of advanced prostate cancer.  Olaparib inhibits the enzyme, poly (ADP ribose) polymerase (PARP), a protein used by cancer cells to carry out DNA repairs.  PARP inhibitors work on cancers caused by a faulty BRCA1 or BRCA2 gene.  Cancerous cells of this type depend on the PARP protein to carry out DNA repairs.  If PARP is blocked, cancer cells cannot repair themselves and die.

Olabarib is the world’s first therapeutic agent approved by the FDA in December, 2014 for the treatment of ovarian cancer patients with mutations of the BRCA1 and BRCA2 genes, which play key roles in DNA damage repair.  Mutations in these genes have been linked with the development and progression of many tumor types, including prostate cancer.  In a recent study published on October 28th, 2015 in the New England Journal of Medicine, researchers found that olaparib is effective in treating the approximately 30% of men with DNA repair defects in their tumors.  This illustrates the principle of precision medicine that one can detect prostate cancers with specific targetable mutations using genomic sequencing to deliver more precise cancer care by matching treatment to those men who are most likely to benefit.  The trial is also very significant in that it exploits the similarities between prostate, breast and ovarian cancers.   In the phase II trial called TOPARP-A, olaparib was found to benefit as many as a third of men (17 out of 49) with metastatic, hormone-resistant prostate cancer, including those who did not inherit cancer genes, but whose tumors acquired defects in DNA repair overtime.  Six men had radiological (CT and MRI scan) responses, and eleven had biochemical responses as evidenced by PSA reductions of greater than 50%.  Four of the patients had responses that lasted for more than 12 months.  Anemia and fatigue were the most common side effects.  Olaparib was determined to be effective in stopping prostate cancer growth, generating lasting decreases in prostate specific antigen (PSA) levels, decreases in circulating tumor cell (CTC) counts in the blood, and radiological responses on CT scans and MRI.  If approved as a new therapy, men would have to undergo genetic testing looking for defects in DNA repair genes in order to qualify for olaparib.  For additional information, see the following linked short article. TOPARP-A, is a major milestone in cancer treatment because it is the first to show the benefit of “precision medicine” in prostate cancer.  Precision medicine is a new, transformative model of healthcare that utilizes information from tumor DNA to match a patient with the most effective course of treatment.  It is conceivable that drugs such as PARP inhibitors could also increase the effectiveness of common DNA-damaging therapies such as chemotherapy and radiation.   For additional information on precision medicine for treatment of certain prostate cancers, see the following linked article published in the OncoTherapy Network.