The Benefits of Genetic and Genomic Testing
Another lab test analyzing serum is called a “droplet digital PCR assay,” and it can also help us determine which patients will best respond to those chemical agents, Xtandi® and Zytiga®. It should be noted that genetic markers are also important in light of the patient’s family history. We want to know what the family history is with regard to other cancers. We can see that a patient’s daughters may be prone to breast cancer or ovarian cancer; and now even colon and pancreatic cancers enter the picture in the spectrum related to prostate cancer. These cancers are essentially on the same page in our genetic makeup. Melanoma is also now seen to be genetically related to prostate cancer, and all of these cancers may occur at increased frequency in the patient tested.
Both Xtandi® and Zytiga® have a side effect profile similar to that of hormonal therapy. With patients for whom Xtandi® and Zytiga® are not effective or are unlikely to be effective as indicated by positive genetic markers (BRCA1 and BRCA2), we may prescribe Lynparza® (olaparib), which is known as a PARP inhibitor (poly ADP-ribose polymerase). Many patients fare quite well with Lynparza®. Another immunotherapy agent, Keytruda® (pembrolizumab) is known as a PD1 inhibitor. We are finding that patients who are not responding well to Lynparza may benefit from Keytruda. We have a growing arsenal of medications at our disposal for patients with advanced or recurrent disease. Both hormonal therapies and immunotherapies are associated with far less toxicity than chemotherapy as they are “targeted therapies”
While genetic testing is important for the patient’s siblings and children, (and also for the patient on occasion), there is even greater importance in sampling the actual cancerous tissue removed from the patient in order to identify somatic mutations. This is known as comprehensive genomic profiling (CGP). This test can help identify exactly which treatment may benefit the patient (e.g. AR-7 mutations suggest resistance to Xtandi®/Zytiga® while HRR gene mutations predict response to Lynparza). Checkpoint inhibitors (e.g. PD-1) suggest sensitivity to pembrolizumab. We have been using FoundationOne ®CDx as the best genomic test currently available for identifying somatic mutations. This test searches 324 genes for cancer-relevant mutations in the DNA.
* To learn more about Invitae Genetic Testing, click here: https://www.invitae.com/en/detect-hereditary-prostate-cancer/?utm_source=DHPC&utm_medium=poster&utm_campaign=fall2019
* The National Comprehensive Cancer Network (NCCN) offers patients recommendations on genetic testing and describes Medicare coverage here: https://myriad.com/products-services/hereditary-cancers/myrisk-hereditary-cancer/
* Additional information on the FDA approved FoundationOne ®CDx Test is available here: https://www.foundationmedicine.com/test/foundationone-cdx