Defective BRCA genes are well known for their ability to cause breast and ovarian cancers in women. But these same gene defects are also strong risk factors for aggressive prostate cancer in men. About 10% of men with metastatic prostate cancer — meaning cancer that is spreading away from the prostate — test positive for genetic mutations in BRCA genes. Fortunately, these cancers can be treated with new types of personalized therapies.
In May, the FDA approved two new drugs specifically for men with BRCA-positive metastatic prostate cancer that has stopped responding to other treatments. One of the drugs, called rucaparib, was approved on May 15. The other one, olaparib, was approved on May 19.
Both drugs work by shutting down the cancer cell’s ability to fix its DNA. Like all cells in the body, cancer cells are bombarded every day by free radicals, low-level radiation, and other stressors that cause DNA damage. BRCA genes ordinarily fix that damage so that cells can function normally and survive. But if the genes are defective, then the damage piles up. BRCA-positive tumors get around that problem by deploying an alternate DNA repair gene called PARP. Rucaparib and olaparib both inhibit PARP, leaving cancer cells without any way to fix their increasingly mangled DNA; eventually the cells die.
The drugs had each been approved already for other BRCA-positive cancers, and prior to their approval were given “off-label” to men with prostate cancer as well. The approvals “should ease some of the previously existing insurance barriers for coverage, enabling more patients to benefit,” says Dr. Marc Garnick, Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org.
What the studies showed