An ongoing early clinical trial in the UK is using a “liquid biopsy” to individualize treatment for advanced prostate cancer in patients who have BRCA genetic mutations.
The researchers are studying a new 3-in-1 blood test as a way to identify patients who are good candidates for PARP inhibitors, such as olaparib. PARP inhibitors prevent cancer cells from repairing their damaged DNA, and thus the cells die.
While PARP inhibitors can be effective, not all men respond to PARP inhibitors, or their cancers mutate and develop resistance to the treatment. This study aims to address the issue of more precisely selecting—and monitoring—patients who will respond best to olaparib. A major advantage of using a blood test for this task is that it is noninvasive.
The blood test has three functions. First, it checks a man’s DNA to see if he would benefit from treatment with PARP inhibitors. Olaparib is especially successful in killing cancer cells that have damaged DNA repair genes such as BRCA1 or BRCA2.
Second, the test analyzes the patient’s blood after he starts treatment to determine if the treatment is working. If it is not working, the patient can switch to a different treatment. For patients who responded well to olaparib, the test showed a nearly 50% reduction in the levels of cancer DNA in the blood after only 8 weeks of treatment. These men lived an average of 17 months after starting the treatment. Comparatively, men who did not respond well to the treatment had an average 2% rise of cancer DNA in their blood, and they lived an average of only 10 months after starting treatment.
Third, the test allows physicians to monitor the cancer’s DNA to see if the cancer cells are developing resistance to the drug treatment. In patients who stopped responding to olaparib, the blood test showed that the cancer cells had acquired new genetic changes that cancelled out the original errors in the DNA genes, thus signaling that the treatment would stop working.
At this time, the liquid biopsy is being tested in only 49 patients. But, the researchers hope their work could lead to olaparib becoming a new standard of care for patients with advanced prostate cancer who meet the genetic criteria.
Cancer Discov. 2017 Apr 27. doi: 10.1158/2159- 8290.CD-17-0261.