PARP Inhibitors
The second transformation in prostate cancer care arose from surprising results of tumor gene sequencing.
“A number of VA investigators involved in the study of metastatic prostate cancer found one actionable type of mutation that we didn’t know about in prostate cancer,” Montgomery said. “Sequencing showed an unexpected number of tumors contained variants like BRCA that are involved in DNA repair.”
About 20% of prostate cancer tumors have a DNA repair defect that could make them responsive to poly (ADP-ribose) polymerase inhibitors.
PARP inhibitors have demonstrated high response rates and improved outcomes in other cancers with high rates of BRCA mutations. Now, those drugs are being tested in prostate cancer, with active participation by the VA.
“Veterans contributed very actively to the PARP olaparib trial, but it’s not the only trial veterans participated in. We’re supporting these studies in a networked way, with three Phase 3 studies at the same time,” said Michael Kelley, MD, national program director for oncology at the VA and professor of Medicine at Duke University. “That level of involvement speaks to the size of the VA population and to prostate cancer as the No. 1 cancer in veterans.”
VA centers were among the highest accruing sites for a recent study comparing olaparib to abiraterone, Montgomery added. The results of that study should be presented in the next few months. Veterans have also participated in Phase 3 studies on rucaparib, niraparib and veliparib.
“Many researchers think that PARP inhibitors may be the most important treatment for many of these men” with DNA repair defects,” Montgomery said. “In some studies with men who have been heavily pretreated, the response rate has been as high as 90%.”
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