Alicia Morgans: Hi, this is Alicia Morgans, Associate Professor of Medicine and GU Medical Oncologist at Northwestern University in Chicago, Illinois. I am so thrilled to have here with me today, a friend and colleague, Dr. Neeraj Agarwal, who's a Professor of Medicine at the University of Utah School of Medicine and the Huntsman Cancer Institute, as well as being the Director of GU Oncology there. Thank you so much for speaking with me today, Neeraj.

Neeraj Agarwal: Thank you for having me, Alicia. It's always a pleasure.

Alicia Morgans: Always a pleasure for me too, even when we have to talk about things that are really challenging, which is what we're going to talk about today. Really understanding how folks in Salt Lake City and Utah in your group, are being affected by the COVID-19 pandemic. Can you tell us a little bit about what you and your team and your patients have been experiencing?

Neeraj Agarwal: Absolutely. So, obviously we have been very fortunate in terms of having the incidents of COVID infections in Utah in general, but that doesn't decrease the value of all the social distancing and making sure our patients remain safe. And that's why I think they are safe so far. So all the issues which are impacting any other hospitals elsewhere on the planet are also affecting us. So I think the number one priority for us is to allow our patients to not visit the hospitals and clinics as much as we can. And that brings telemedicine in play. I don't think I've ever valued telemedicine as much. It was always something like a phone call to my patients and I was always hearing that telemedicine will be more of a player in two or three years from now, but as we always say, crisis brings in or expedites innovation. And I think telemedicine is here, now, in full swing, in full force. And I don't think it is going to go away anymore. Telemedicine is a part of us, for the rest of our lives and for the rest of our clinical practice of medicine.

So I think as I said, Alicia, any person, any patient who can avoid a visit to the hospital, we are trying our best to do that and whether it is a phone call or a video call, we are doing everything we can. Regarding the phone call versus video call, as you know, Medicare has come with the policies where, first of all, it was a very welcomed step by Medicare and CMMS to allow reimbursement for these telehealth visits. So that is a huge deal, as you can imagine from the financial perspective. It has already hit the hospitals and clinics so hard across the country. I think that was a very welcome step to have telemedicine being reimbursed. Now, video calls are reimbursed better than telephone calls. Also, we get to see our patients, which I think patients like it better.

So we are using several video platforms, including the video platform from Epic, but anything which works in the clinic, I'm trying to use that. The Epic connection can be slow many times. Sometimes it takes 15 minutes just to connect with the patient. The patient may not be using the Epic platform, especially older patients who are in their seventies and eighties, who are not even using emails, how can we expect them to connect with us on video through Epic? So I think that actually has prompted us to use other platforms. And I think one particular platform, I would really like to give a shout-out is Doximity. I always used Doximity to connect with my patients in the past, using the phone app, but I think their video app has been superb and I personally think that has been very helpful. But if even that doesn't work, I just do FaceTime with my patients. Many of them have my cell phone number already, so I don't see any problem. And many patients who do not even have a smartphone, I think in those patients we go with a telephone call. So, overall, this is about connecting with the patients, using video calls, or telephone calls.

The second aspect I think is how can we do that always or may not do that always. So, some patients who are coming to the hospital, they have to come to the hospital, regardless. So we are seeing them in the clinic, such as patients who are getting immunotherapy infusions or even getting chemotherapy which cannot be avoided at this time. They are coming to the hospitals and we are seeing them. Patients who are coming to the hospital for scans, which cannot be delayed or injections with Lupron®, many patients who are staying close by, they like to come into the hospital for their androgen deprivation therapy injections that either are GnRH agonist or antagonist, we end up seeing them in the clinic.

So, first of all, my first priority is to keep myself safe so that I can keep my patients safe and can take care of them. So, the second part is, what we are trying, what we are doing to keep our patients safe when we are seeing them in the hospital or even health care workers safe, I think if we get infected, nothing can be worse than that. I cannot even imagine if I can get infected and if I'm an asymptomatic carrier, how many patients of mine may get infected from me, so that's how I look at this.

The first thing I want to do is to keep myself protected. Fortunately, my hospital has a policy that every single person entering the hospital main door or through any door of the hospital, they have to go to thermal scan and if they have any temperature, regardless of the cause, they are not allowed to come into the hospital. In addition to that, every single person entering the hospital has to go through a questionnaire. This is a brief questionnaire, mostly verbal, but it basically covers any contact with a COVID-19 carrier or a potential COVID-19 infected person, such as any symptomatic the patient, whether a patient has symptoms or not, and in case of patients having symptoms, we usually send them for testing, unless patients are very sick and they cannot wait for testing, and there is a separate triage protocol for those patients.

Regarding patients who have allergy, sometimes it is a time of allergies, a lot of pollens, spring right now, it is not very unusual to see allergy symptoms. And I think that's where the challenge comes. Patients are sneezing and coughing, sometimes it is very difficult to figure out whether they're really symptomatic with COVID-19 or it could be a simple allergic reaction. And that's where the testing is playing a more important role than ever. So, fortunately, we have surplus testing available. ARUP Lab is a part of the University of Utah and they are a national reference laboratory that has developed testing for patients from across the country. So I think having ARUP Lab here is a huge asset and we are able to test as many people as we want. So I think that's a huge ideal for us, a huge privilege for us to have that kind of lab right here in our vicinity.

Alicia Morgans: I totally agree with you about telemedicine and some of the opportunities and things that we can see, particularly with video conferencing. I know I, personally, have had some challenges in our clinic and you mentioned that it can take some patients a long time to connect. Are there challenges that that make video telehealth that you've experienced in video telehealth or in telehealth generally that you wanted to mention?

Neeraj Agarwal: Absolutely, yeah. Yes, so patients, first of all, taking a step back, patients always prefer to connect on video so that they can see us and we can see them. It's always better than talking to them on the phone, but I realize that most of my patients are older patients, elderly patients. As we know, cancer is more prevalent in the elderly population and many of my patients don't even use emails. Patients who are living far away from cancer centers in their ranches, farmhouses, very simple, great people, but they do not have access to technology. They May not have high-speed internet connection because they don't use that, they don't need that. And that's where challenges come as far as video consulting is concerned. Connecting with them can become a time-taking task. Sometimes it takes 15 to 20 minutes to connect with a patient.

And if you take into account the number of patients we see at a given point of time in our clinic on a given day, even with telehealth, we have 20 to 25 patients scheduled in our clinic. And if you have to spend 15 to 20 minutes in just connecting with a patient, to be able to see the patient, I think that can take a toll. And by the end of the day, you are already behind by many patients. And I think the simplest solution for those situations is to just avoid video visits and go straight to the phone call and complete the visit. That has been my policy so far.

Alicia Morgans: Well, and that makes sense and certainly I think there's an opportunity for us as a field to make progress in this area because we really had not planned on doing any kind of telehealth at this point in time in such a large scale. So, I'm glad that it's predominantly working for you and for others around the world, but it's also so important that we identify areas to improve, and so I appreciate you sharing that. You know, some people have talked about clinical trials being particularly hard hit as well during the era of COVID-19 and as we try to limit patients' engagement in the clinics, then certainly we may be limited in terms of support staff or in opportunities to undergo additional testing for screening. Have you experienced this in Salt Lake City and how are you moving past it as hopefully, the wave of COVID-19 is starting to diminish?

Neeraj Agarwal: Yes, that's a great question, Alicia. So we cater to the pretty much entire Intermountain West and for our patients, it's not very uncommon to see patients driving for six to seven hours just to see us, and that's where clinical trials become very challenging because we have to follow the protocol-defined schedules. We have to see them in person. We have to do the AE attributions, especially for registration trials. We always look forward to positive trials, but positive trials also bring along, themselves, with the FDA audits and that can become a nightmare if you have patients who are not even being seen in the hospital, for any reason. Here, COVID-19, but for any reason. They may be sick, they may be sick for another reason, so clinical trials inherently have their own challenges, which becomes even more challenging in situations like this. So, fortunately, multiple registration trials have allowed telehealth visits with protocol amendments.

Even that has brought in a lot of challenges. Think about amending one protocol. Now, let's think about amending a hundred protocols. We have the same number of CTO staff, the same number of regulatory staff, and now they are certainly working on amending a hundred clinical trial protocols at the same time and I think that has been quite challenging. We are basically trying to make it work, as much as we can. Struggling many times, I will be very honest with you. Nothing is a hundred percent perfect, but I think our institutional review board has been very supportive, from that perspective, sometimes just allowing us to deviate and knowing that a technical amendment may not be possible in a three-day time, so we have been allowed to deviate and report to the IRB after deviation when a patient cannot make it to the hospital.

It has also been very challenging for the sponsors. I cannot imagine a registration trial that has opened in 27 different countries across five continents. It is very challenging for them because every place has different challenges associated with it. We can talk about bigger cities versus smaller towns. I think the challenges are very nuanced. I think I feel for sponsors of large registration trials right now, about how they are able to even survive, leave aside taking care of all the challenges.

There is another aspect that comes when you are comparing a standard of care drug with a new drug or combination which requires infusion therapy. So I won't name a particular clinical trial here, at this point of time, but just for the sake of discussion, let's talk about a given clinical trial, but a standard of care drug is an oral therapy which can we take it continuously nonstop, without the patient having to come to the hospital. But for the infusion therapy arm, patients have come to the hospital at least once in three weeks or maybe multiple times a month. And if patients are not able to make it to the hospital to get those infusions, I cannot imagine what kind of bias it will introduce for the trial and what kind of imbalance will happen between the arms, when on one arm, oral therapy is continuously being given without any problems and on the other arm, the experimental arm, the infusion therapy cannot be given because patients cannot make it to the hospital.

And I think the best strategy, in this case, is having to stop enrollment on the trial. We cannot do anything with patients who are already enrolled and already getting therapy, but patients' new enrollments have been stopped on those trials. But I think these are the challenges we are seeing on a regular basis regarding clinical trial patients and clinical trials in general.

Alicia Morgans: I totally agree and was thinking earlier today about some patients on one of our clinical trials and like you, I won't name a specific clinical trial, but these patients are still on study, but they're actually refusing to come in for their scans because they're concerned about exposure and they live very far away because the catchment area is similar to yours, particularly for this given trial, was very large and people would drive four or five hours in order to get in to get the access to the therapy. And I do think that we may see, for some of these studies, that it's possible that we couldn't be introducing bias simply because we are not doing the scan, so we don't actually know when true progression happens.

It could have already happened and my hope is, for these patients, that they have not been progressing and they don't symptomatically seem to be progressing. But we know patients can have radiographic progression without having symptoms, which is why we have scheduled scans. And so the bias that could be introduced even in patients who are already on study, is concerning and it's actually unclear which direction it may bias the study and every study could be a little bit different. So, lots of challenges with clinical trials that I am hopeful we'll be able to move past, but I appreciate certainly you raising them and talking that through.

And as you're treating patients on standard of care options, are there any areas in GU medical oncology where you're specifically facing differences in some of the decisions that you may have made before, now that COVID-19 comes into the decision-making?

Neeraj Agarwal: Yes. So for example, for the sake of discussion, let's talk about kidney cancer. Fortunately, because of the tremendous advancements in metastatic RCC, we have drugs that none of them are really immunosuppressive. They will never work, but we have effective drugs which are not immunosuppressive, so whether it is a VEGF TKI or a VEGF TKI or multi-tyrosine kinase inhibitor or immune checkpoint inhibitor, I think all of them are very safe, in my view, and we have been using them. I think the challenge comes where we were trying to minimize the visits of these patients to the hospital. And in those patients, in new patients who are newly-diagnosed metastatic RCC patients, I'm tending to start them on an oral therapy, oral pill for now, so as to minimize the visits for infusions to the hospital.

We just heard the press release on the FDA approved a six-week dosing of pembrolizumab at 400 milligrams every six weeks. I personally thought it was a very welcome thing to happen in such a gloomy atmosphere. Otherwise, I immediately changed many of my patients who are getting axitinib pembrolizumab combination or I'll change them. It was just yesterday, so I'm going to change those patients to every six-week infusion. But, otherwise, I think I'm leaning towards more like using oral pills or VEGF tyrosine kinase inhibitors in these patients who are newly diagnosed. For patients with metastatic prostate cancer, decision-making is not as simple because there is a, as you know better than anyone, Alicia, there is a direct competition or both class of drugs, chemotherapy with docetaxel, versus androgen signaling inhibitors are considered equally good options in metastatic castration-sensitive prostate cancer.

And we have always debated pros and cons of chemotherapy versus those oral pills targeting androgen signaling, but I think at this point of time, a decision is pretty straightforward. I have not been using oral chemotherapy with docetaxel for any of my patients who are newly diagnosed metastatic castration-sensitive prostate cancer patients. As a rule, we are using oral therapies. Even on oral therapies, I'm tending to use more apalutamide and enzalutamide over abiraterone because abiraterone lately required lab checks for at least the first two months, every 15 days, for liver function tests and so on. And that makes me lean towards the direct androgen receptor inhibitors such as enzalutamide or apalutamide, which really do not require any lab testing.

In the context of metastatic CRPC setting, again, I'm trying to push out chemotherapy as much as I can. It becomes especially challenging for patients who are progressing on androgen signaling inhibitors and really the only option they have is either docetaxel or cabazitaxel and that becomes really challenging. So, in patients who have slowly rising PSA level, scans are not progressing very rapidly, I'm trying to push out chemotherapy in those patients as much as I can. But obviously in symptomatic patients when I don't have any options who have high volume disease and I don't have any option but to start them on treatment, I'm using growth factors, G-CSF, more often than before for those patients.

So any patients who are starting docetaxel or cabazitaxel, I'm leaning towards using G-CSF regardless of what guidelines say right now. Anyone who is 65 years old and plus. So, those are the things I think I'm trying to do and not do in taking care of these patients with metastatic RCC and metastatic prostate cancer.

Alicia Morgans: I think that's really helpful and I think that's certainly mirrored by the practice patterns for a lot of people that I have talked to in certainly my own practice. It's interesting we find ourselves, for patients who have bone-only metastatic disease, for example, using radium earlier for some patients than we might necessarily have. We have a lot of patients who are interested in sip-T, as well. I don't love the interactions, necessarily, with having to go to multiple places to get apheresis and then reinfusion for that particular modality, but certainly, it shouldn't cause immunosuppression and so has been an option for some of our patients as well.

So, really thinking about trying to use the whole spectrum of mechanisms of action in mCRPC, it's always a focus but we do think about it a little bit differently in the era of COVID-19, so I sincerely appreciate your insights and your time. Do you have any overarching messages for the listeners as we wrap up and as they're trying to make sense of how to move forward in this strange time?

Neeraj Agarwal: I think just a concluding statement, Alicia. I think a lot of good things will come out of this crisis, such as telemedicine. That will be number one. And I think we will find new ways to interact with our patients and see them over time. So I think that would be my final take from this crisis and I want to wish best of luck to all my colleagues across the planet and different countries who have not been as fortunate as we are in Salt Lake City. Thank you very much.

Alicia Morgans: Thank you. And I wish the same to those around the world as well as their patients, families, loved ones, everyone, we just hope you take care and thank you for listening and thank you for your time, Dr. Agarwal.