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.


Prostate Cancer Diagnostic Testing Menu and MRI Review.

I recently came across the following menu of prostate cancer diagnostic tests offered by a specific facility.  The tests are mainly used to identify those cancers that may be aggressive requiring further biopsies or treatment.  The first group of tests would be applicable to men whose PSA values indicate the possibility of cancer while the second group are biopsy-based.  This information should be discussed in conjunction with your personal physician and your personal insurance carriers as to need for the tests, their availability, costs and insurance coverage.  Information concerning these tests is also available in earlier blogs on this website.  To find them, simply insert the test name into the search engine on the home page.  In addition, the latest edition of the Prostate Cancer Research Institute (PCRI) Insights (see link) contained an excellent review article discussing all the current prostate MRI techniques

Post-PSA Diagnostic Testing:
4K Score: This test measures four prostate-specific kallikreins in the blood: Total PSA, FREE PSA, Intact PSA and Human Kallikrein 2 (hK2). Results are combined with patient age, digital rectal exam (nodule, no nodule) and prior negative biopsy results (yes, no). The tests then provides a % probability on a scale of 1%-95% for the patient having high-grade prostate cancer. The 4K Score is designed specifically to reduce the number of unnecessary negative biopsies that detect low-grade cancer. This means not all men who have an elevated PSA will require a biopsy.

PCA3 Score: This is a simple urine sample collected following a digital rectal exam for the determination of the PCA3 score. Specific for prostate cancer, and, unlike the PSA, this test is not affected by prostate enlargement or other non-cancerous prostate conditions. In combination with PSA and digital rectal exam (DRE) results, the PCA3 score provides useful information to help decide if a biopsy is needed, or can be delayed. It’s much more specific in giving additional information about the aggressiveness of the cancer if the patient has a positive biopsy.

Post-Biopsy Genetic Testing:
MRI-Guided Biopsy: An MRI-ultrasound fusion biopsy involves taking an MRI and then fusing the data with real-time ultrasound images for guidance on biopsy procedures. While there are several types of MRI-guided biopsy techniques, one such system, the UroNav Fusion Biopsy System combines electromagnetic tracking and navigation with an onboard computer and a real-time imaging interface in one mobile workstation. The MR/Ultrasound fusion aligns and registers prior diagnostic MR images with real-time ultrasound images.  For a more comprehensive MRI review, see the following link.

Oncotype DX: The Oncotype DX Genomic Prostate Score is a biopsy-based genetic test that can be combined with other measures to predict the aggressiveness of prostate cancer. The test applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions for each individual patient. The test is a multi-gene RT-PCR expression analysis developed to work in combination with prostate needle biopsies. It measures the expression of 12 cancer-related genes representing four biological pathways and 5 reference genes, which are then combined to calculate the Genomic Prostate Score (GPX). This biopsy-based score has been clinically validated as a predictor of aggressive prostate cancer. Three studies presented at the 110thAnnual Scientific Meeting of the American Urological Association this year showed this test improved risk assessment for patients and reduces cost of prostate cancer care. This test also is helping to examine further the biology and development of prostate cancer in African American men who are at a high risk for the disease.

Prolaris and Genomic Prostate Score: The purpose of this score is to distinguish between aggressive cancers that need treatment and those that are slow growing and may need active surveillance. The Prolaris Score is a measure of how fast a prostate cancer tumor is growing after a biopsy has indicated its presence in the prostate gland. Biopsy tissue samples are used to determine a patient’s personal Prolaris Score. It measures how fast cancer cells in the tumor are dividing. Measuring a 46-gene expression signature, Prolaris also includes cell cycle progression genes selected based upon correlation with prostate tumor cell proliferation.

Confirm MDx: A genetic test rooted in the field of epigenetics, identifies key changes in gene activity for a negative biopsy or results showing high-grade PIN or ASAP. ConfirmMDx was developed to help reduce unnecessary repeat biopsies through its support of the negative predictive value (NPV). Clinical trials showed this test to be the most significant independent predictor for prostate cancer detection on repeat biopsy. A risk score for ConfirmMDx methylation-positive men was developed to increase the positive predictive value (PPV), which helps identify those with aggressive prostate cancer. This test combines these risk scores along with epigenetic profiling and strongly correlates with the detection of aggressive prostate cancer upon repeat biopsy.

Men Who Speak Up

Bayer HealthCare is a strong proponent for men speaking up about prostate cancer.  They recently sponsored a symposium on the subject in which I participated.  If men were more vocal, prostate cancer funding hopefully might increase following the example of women who are such excellent communicators about breast cancer.  The linked Bayer HealthCare site provides video and written information about advanced prostate cancer specifically and a movement entitled Men Who Speak Up.

Information on Prostate Supplements and PSA Testing

The Prostate Cancer Foundation (PCF) publishes a highly recommended e mail periodical entitled NewsPulse to which one can subscribe.  The October issue contained two articles which I will simply summarize and link.

The first article concluded that popular prostate supplements such as those containing saw palmetto do not benefit prostate cancer patients.  They do not decrease the risk of spread of localized disease, affect survival or lower the risk of side effects from radiation therapy.  The supplements offered no benefits related to prostate cancer outcomes.  However, it should be noted that the article did not address the issue of prostate cancer prevention.  The subjects in the study were all prostate cancer patients.  As an editorial note, I would not include pomegranate  extract in this group of supplements as some positive effects on prostate cancer and PSA doubling time have been observed with the extract (see April 4th, 2011 blog post).

The second article cited a study concerning the effects of the relaxed PSA testing guidelines issued in 2011 by the U.S. Preventative Services Task Force.  The current study results indicated that such relaxed screening may delay the diagnosis and treatment of aggressive prostate cancers.  Men who could have been eligible for treatment and perhaps cured of more advanced prostate disease may be diagnosed too late.  Since 2011, PSA screening has decreased by 28%.  The 2011 guidelines did have a positive effect in that diagnoses of new, low-risk cancers dropped by 38%.  However, researchers also found a drop of 28% in diagnoses of intermediate-risk cancer and a 23% drop in diagnoses of high-risk cancer one year after the guidelines were published.  These finding were consistent with what the researchers hoped would not happen.  They concluded that “men will develop more advanced prostate cancer before it is diagnosed and be less likely to be cured.”