Daniel Kwon: Thank you so much for having me today.
Neeraj Agarwal: So we'd like to discuss, Daniel, your trial in progress on germline testing of patients with prostate cancer in this unique setting where you don't have to worry about insurance status of the patients. Before we get into this topic, please tell us about your viewpoints on germline testing of patients with locally-advanced or metastatic prostate cancer, or even localized prostate cancer. We all know that this is a huge problem in the real world. Patients are just not getting tested despite the fact that we know many of these patients are carrying these mutations, which have implications on their families, siblings, children. So please tell us about the background. What prompted you to do this trial?
Daniel Kwon: That's right. It's quite simple. I was seeing patients in my clinic, both at UCSF and the VA, who are just not getting tested for one reason or another. And meanwhile, year by year, the indications for getting tested and the treatment implications are expanding. For example, with last year's FDA approval per the AMPLITUDE study. We needed to think of ways to improve testing. We saw that in our own VA dataset that only 13.4% of patients had germline test orders and were getting completed, which is far from the near 100% that should ideally be tested. Of course, some patients are going to naturally decline for one good reason or another, but we should be getting close to 100%.
Neeraj Agarwal: 4% is very low. And I must tell you that real-world data out there is not that different. Even NGS testing, based on which we have multiple approvals, such as pembrolizumab for MSI-high, TMB-high mutation status. We have ARPI-PARP inhibitor doublets. We have monotherapy PARP inhibitors now approved for several years, and patients are not getting testing. And NGS testing has implications on patients' care, patients' own care, but to go beyond that, go to germline testing and knowing that many of these patients who have NGS testing, positive mutations, mutations present on NGS testing, a substantial number of these patients have germline mutations. And as we discussed, it can affect their family members, their daughters, their sons, their siblings. What prompted this study? And please tell us more about this study. How are you conducting this? Where are patients, if they want to, can they enroll in this study? And what are the logistics of enrollment into this study?
Daniel Kwon: Right. And I totally agree with what you said. It's beyond treatment implications when it comes to germline testing. It's that it can have implications on family members, both male and female, and potentially even preventing cancer for them in addition to identifying cancer early. And so it is critical in not just the patient, but family. What led us to conduct this study and design it was we were, again, noticing low rates relatively of germline test orders. Meanwhile, we also had data at the VA that with the, quote unquote, mainstreaming efforts that were expanding, and mainstreaming refers to oncologists directly ordering germline testing instead of referring to genetics, that mainstreaming was associated with more timely and efficient use of genetics germline testing in patients who are eligible. However, mainstreaming was just not being adopted to high degrees by oncologists. And so based on other data, there was a ton of qualitative data done by Dr. Schoener's team that showed a number of barriers and facilitators to mainstreaming at the VA, we developed a matched set of implementation strategies directed at oncologists to help them and support them and facilitate mainstream germline testing.
There were three particular strategies we developed, and one is developing an educational guide to have in educational materials, resources, and tools at the VA to support and educate oncologists at the VA. The second is something called audit feedback, which is a particular strategy that involves assessing and measuring an individual oncologist's performance when it comes to germline testing and comparing it to benchmarks and feeding that back to the oncologist so they know where they're at compared to peers. And then the third and last strategy we developed is something called external facilitation, where we have a genetic counselor who's trained in both the logistical and clinical aspects of germline testing to be available and check in on oncologists. The way this trial is designed is that we don't roll all these strategies out at once. Rather, it's sequential. We start with the guide. Those who do respond to the guide continue with the guide, and those who do not respond to the guide get put into a separate cohort where they receive the audit feedback. And then we have another cycle here where those who respond to the audit feedback continue with the audit feedback, those who do not then get randomized one-to-one to either continue audit feedback or have audit feedback plus external facilitation. We had to develop some sort of measure of what defines a response, and so we developed this benchmark criterion mostly based on feasibility and getting enough power and a sample size of 35% or more of their orders being mainstream for those eligible patients with metastatic prostate cancer. At the end of all of this, we're going to see...
This is a cluster-randomized trial in that the clusters are oncologists, but we're looking at patient-level germline test orders. We're going to see if there's a difference between the group that was randomized to audit feedback or audit feedback plus external facilitation among a host of other measures, such as actual completion rates of germline testing, adoption, reach, other measures using our RE-AIM framework, which stands for reach, effectiveness, adoption, implementation, and maintenance. And we're doing interviews along the way as well over these two years that the project is being done where we interview oncologists and see what was working, what was not, what were the barriers and facilitators, how could we further improve our processes.
Neeraj Agarwal: And we're really hoping that all these measures will ultimately lead to all oncologists ordering germline testing for our patients with advanced prostate cancer.
Daniel Kwon: Yeah, certainly. I hope so too. And that way, we can ensure that such precision oncology technologies, there have been huge advancements over the past decades with the speed and cost of next-generation sequencing, it actually reaches patients and the patients actually benefit, as do their families.
Neeraj Agarwal: I agree with you 100%. Well, thank you for sharing your insights on germline testing of patients with advanced prostate cancer. And congratulations for conducting this very pertinent trial, the results of which we hope will impact how our patients across the world will benefit with timely germline testing. Thank you for being here today.
Daniel Kwon: Thank you. Thank you for having me.