Recent approvals of PARP inhibitors mark the beginning of precision medicine for prostate cancer. Through patient case scenarios, Drs. Lisa Holle (Oncology Pharmacist, University of Connecticut) and Pedro C. Barata (Medical Oncologist, Tulane University) dive in-depth into appropriate use of olaparib and rucaparib in clinical practice, including patient and disease factors to consider. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us   TRANSCRIPT [MUSIC PLAYING]   ANNOUNCER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] LISA HOLLE: Welcome to the e-learning ASCO podcast on PARP inhibitors in prostate cancer. I'm Lisa Holle. I'm an associate clinical professor at the UConn School of Pharmacy, and I practice at UConn Health's Carroll and Ray Neag Comprehensive Cancer Center in Farmington, Connecticut. I'm joined today by Dr. Pedro Barata from Tulane University, New Orleans. PEDRO BARATA: It's great to be here with you. LISA HOLLE: Same here. PEDRO BARATA: So, Lisa, I know we'll be talking today about PARP inhibitors in prostate cancer. And it's kind of a kickoff, you know. What do approvals of the different PARP inhibitors for patients with advanced prostate cancer mean to you? LISA HOLLE: Yeah, this is a really exciting time in prostate cancer, because this is really the introduction of precision medicine in the treatment of metastatic castrate-resistant prostate cancer. So this is a group of patients, traditionally, who can benefit from PARP inhibitors that have not had good responses in the past to our traditional treatments. In fact, it really does allow these patients who would be eligible to receive PARP inhibitors to have an extended time on active therapy. Now, as we know with metastatic castrate-resistant prostate cancer, we can't cure the patients, but we can extend that time that they're on active treatment. In fact, in the two studies that were conducted, the PROfound study evaluating olaparib, and the TRITON2 study evaluating rucaparib, the progression-free survival time on average was about eight months. And in the PROfound study, which compared it to our new generation hormone therapies, that really doubled the progression-free survival time. And recent overall survival time was also improved by about five months. So this is really a significant advancement for these patients. And it really underscores the need that we have now for our metastatic patients to do germline and somatic mutation testing to see if they might be eligible for these treatments in the future. So Dr. Barata, who do you think could best benefit from the PARP inhibitors in prostate cancer? PEDRO BARATA: Yeah, and also, it's a great question, by the way, great introduction to the topic. And you indeed touched on something very, very important. And I think it's a perfect segue way for your question, which has to do with can you identify the good actors or the patients who are likely to respond, right? So when you think about how these drugs were developed, if we started by classifying this group of genes known as DNA repair genes, right, who have this job or function of repairing defects at time of cell replication. And so among these different genes, we start talking about BRCA, BRCA1, BRCA2, ATM, CDK, you know, RAD51, FANCA, et cetera. And so it seems like patients who harbor a defect in one of these genes are actually more likely to respond to these therapies. And these therapies, by the way, they inhibit the PARP and the enzyme that helps with burying the DNA, if you will. And so, you harboring a defect in one of these enzymes actually helps you to