Considerations of GU Cancer Patients Treatments in the New Reality of COVID-19 - Petros Grivas

March 19, 2020

Recorded Date: March 18, 2020

Petros Grivas, Brian Rini, and Ali Khaki discuss the current status of the COVID-19 global pandemic and its impacts on the current ongoing care for patients receiving treatment for cancer and for patients currently on clinical trials. It is clear that there is no data on oncologic outcomes as the virus is rapidly spreading.  Drs. Rini, Khaki, and Grivas discuss aspects of treatment selection and treatment decision-making for each patient. 

Drs. Rini and Khaki also provide evolving details of the COVID-19 and Cancer Consortium Registry. This is a multi-institutional registry which is a collaborative effort set up to capture cancer patient data who have been diagnosed with the coronavirus or suspected of having this virus also being treated for cancer.


Brian Rini, MD, Clinical Trials Director, Vanderbilt University

Ali Khaki, MD, Hematology/Oncology Fellow, Fred Hutchison Cancer Research Center, University of Washington, Seattle, Washington, United States

Petros Grivas, MD, Ph.D., Associate Professor, Clinical Director of Genitourinary Cancers Program, University of Washington, Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center

Related Content:

View: COVID-19 and Genitourinary Cancers Videos

Read: The COVID-19 & Cancer Consortium (CCC19): A Collaborative Effort to Understand the Effects of COVID-19 on Patients with Cancer

Read the Full Video Transcript

Petros Grivas: Good afternoon, I'm Petros Grivas. I'm a medical oncologist at the Seattle Cancer Care Alliance and Associate Professor at the University of Washington. I'm here today with a couple of esteemed colleagues and I'm very happy to have the opportunity to discuss with them. Dr. Brian Rini, who's a Professor of Medicine and Oncology and the Chief of Clinical Trial Office at the Vanderbilt University, and also Dr. Ali Khaki, who is a third-year fellow in hematology-oncology at University of Washington and Fred Hutchinson Cancer Center. Brian, Ali, welcome.

We'll start with the obvious questions here. We have to make rapid decisions every single day in the clinic. We have many patients with genitourinary cancers. We'll start with you, Brian. How do you think about, what's your kind of mindset? How do you balance this emerging crisis with COVID-19 in the context of patients who need treatment for genitourinary malignancies? What's your conceptual framework about that? And then Ali can comment afterward.

Brian Rini: Sure, thanks. Yeah. I think like most centers and most of the guidance, regulatory and otherwise, that's come down, we're all trying to keep people away from the medical centers as much as possible. So we've all taken a hard look at our patients, either on or off trial, and asking ourselves, "Do they really need to be in the building?" If they're just doing simple toxicity checks, they're not getting infusions or scans or have sort of critical visits. And we're delaying those visits, pushing them out, trying to do a lot of telehealth which rolled out this week at Vanderbilt, and I know other places and is now a little bit easier to do with the federal emergency declared. So we're trying to keep people away as much as possible and do things at a distance. And that's a priority and it takes some getting used to and some operational considerations.

For patients on trial, it's a little bit more difficult. A lot of them have infusions and other visits, and there was just some FDA guidance issued today around that. So, as you say, it's changing day by day, hour to hour. I think in medicine we're used to dealing with rapid information, but I've never experienced it at this rapid a pace, on an almost an hour-to-hour, day-to-day recalibration of how we approach patients.

And then just a specific note in terms of GU cancers, I think we're taking each situation in each cancer differently. So if it's a frontline renal patient, how are we approaching them? We're certainly observing many more of them. Even though I did that a lot, probably observing more of them. And at least trying to defer the start of therapy. What we don't want to do is start therapy that's going to land people in the hospital sooner and expose them to a higher risk. So it's just a different calculus in that benefit-risk equation.

Petros Grivas: Absolutely. And Brian, you have led trials regarding active surveillance in patients with low risk, low burden of renal cell carcinoma. And it sounds like that in the current scenario the data you generated may be a little bit applicable. It's a little bit higher risk, but of course carefully in a calculated way. 

Brian Rini: Yeah, it's the risk of cancer progressing versus the risk of COVID infection, which I think clearly carries higher mortality in cancer patients. There's not great data, as you know, but I think that's certainly very believable.

Petros Grivas: Absolutely. Absolutely. We'll come back to the data-free zone in a second. I want your opinion on that. Ali, any comments on that, what Dr. Rini mentioned?

Ali Khaki: I think Tom Powles, and I think Dr. Rini, they've done a nice job with the Uromigos podcast, and as well as posting some stuff on Twitter with some additional guidance. I think that I agree with what Dr. Rini is saying, that trying to avoid patients coming to the hospital if they don't need to, or the cancer center if they don't need to. And then trying to be thoughtful about what's actually urgent and needs to be done, versus things that can be pushed off for these weeks or months.

Petros Grivas: How do you guys view the concept of telemedicine and in the context of what Brian, you said, about trying to keep people away from the cancer center, which is very important. How do you view telemedicine evolving with the recent news yesterday, and how is Vanderbilt going to adopt that?

Brian Rini: We're rolling it out widely. I think that the best thing about the federal emergency is it's torn down some of those sort of state-by-state restrictions. So I've applied for medical licenses, I think, in four states now. And it was always kind of silly that I was doing the exact same paperwork every time. And so if there's some good that comes with this, I think some of these artificial barriers that have been constructed for various reasons, we might take a hard look at them and say, "Gee, does this really make sense to do this?" Because responding to this crisis is one thing, but we need to prepare ourselves to respond to the next one as well. And clearly, globally, we really weren't well prepared to respond to this. And those sort of state restrictions for telehealth are a small example of that. But we're starting to work through that. We had all talked about telehealth but maybe not done much of it and this is sort of forcing the issue.

Petros Grivas: Do you advocate for patients, Brian, who are on a checkpoint inhibitor therapy for metastatic kidney cancer, urothelial carcinoma? Do you alter the frequency of the checkpoint inhibitor? Do you do it every other dose, do you use a higher dose? Whether it's six weeks or three weeks?

Brian Rini: Yeah, I think it depends on the clinical scenario. So I think anybody who's been on for a reasonable period of time, call it three months, has gotten to their first restaging and has some tumor reduction or control of disease. I think you've got to think hard about just holding all therapy. And something that I know we've been interested in, many of us in the field, about limiting the duration of therapy for IO, absolutely. And again, this is sort of forcing the issue.

So it's hard to give blanket advice, but I think you sort of have a sense of a patient's tumor, patient burden in terms of do they need ongoing therapy or might we be able to take a pause here? Because we don't know where the other side of this is. We hope it's weeks away, but it could be months away. But I think most patients can probably miss at least a dose or two of medicine without harm. Again, that's a guess on my part. I'm not aware of great data, but it's all part of that risk-benefit of continuing versus pausing.

Petros Grivas: And on that note, you led a clinical trial with Dr. Ornstein at the Cleveland Clinic regarding intermittent therapy with checkpoint inhibitor in kidney cancer. Do you want to comment very briefly about that, too?

Brian Rini: Yeah, so we've been interested in not treating people for a while, whether it's an observation of metastatic RCC or intermittent therapy initially with sunitinib, more recently with nivolumab. And so it's all sort of in the philosophy of treating people with as few drugs as possible. And again, there's more of an urgency to do that now, simply to keep them away. Talking with Tom in London, I think they're thinking more about sort of reverting back to VEGF monotherapy as oral therapy, which certainly can be done at home with minimal clinic visits compared to the IV therapies that our IO-based combinations are now anchored to.

So we're rethinking the whole strategy of it. But again, just the ability to... We sort of give therapy as much out of habit as anything else. We've designed trials a certain way. We designed the infusion schedule, and then we sort of just don't necessarily think about changing that in clinical practice. But I think we're going to have to think a lot more about it. And again, I think there'll be some good that comes with this in terms of just different ways of thinking about approaching patients and not making it as burdensome for patients in the long run. So hopefully that comes out of this.

Petros Grivas: I agree with you. I think the situation and crisis will teach us so many lessons and will impact long term how we practice medicine, how we think about clinical trial design. Ali, any comments on that in kinds of treatment of patients with genitourinary cancers with checkpoint inhibitors or chemotherapy?

Ali Khaki: I agree 100% with what Dr. Rini was saying. I think that skipping doses, especially for people who've been stable on it, is a very reasonable approach. I'm also interested in considering alternate dosing schedules, the Q4-week nivolumab, Q6-week pembrolizumab that had been spoken about, considered it for some time. I think that now is an opportunity for us to sort of get more experienced with that. But I defer to both of you guys, who have more experience than I do about what the right patient would be to consider something like that for.

Brian Rini: So one of the things that's sort of come out, Tom Powles and Sophie [Gellison 00:08:28] are publishing some specific guidelines in GU cancer, I think in a European urology journal if I have that correct. And one of the sort of Twitter debates has been about neoadjuvant chemo in bladder cancer and some of the relatively modest benefits. Maybe we shouldn't expose patients to that risk of infection and hospitalization and just coming back and forth for infusions.

And others have argued that, well, cystectomy is a risk in and of itself and maybe the neoadjuvant chemo will push those patients out to two or three months from now when the time is safer. And I'm not sure what the right answer is. And so, you see this disease more than I do. I'm wondering what your thought about that specific topic is?

Petros Grivas: That's a great question Brian, and I think the answer here is very difficult. And we had this discussion with our leadership team yesterday, whether we should develop some guidelines or leave it case by case. I think there are competing risks here with either approach. And my bias is if someone is really fit for chemotherapy, they can get cisplatin. And the challenge, as you mentioned, with operating room right now there is a huge push in our institution to free up operating room space, ICU space. And it's hard to schedule those people for the OR. So even the urologists say if you can safely give this patient chemotherapy and the patient's fit enough, that may be an approach.

Again, this is a calculated discussion with a patient, pros and cons. I had a patient the other day who we had a very frank discussion. And every patient may have a different approach to this. And it's hard to quantify the risk from infection with chemotherapy or surgery. Chemotherapy can suppress the immune system, of course, which is something relevant.

To your point that the totality of the data support neoadjuvant chemotherapy, but the context of COVID-19 should be taken to account in every single discussion. And of course, in patients who are borderline eligible or we could do it, but maybe those people may forgo the chemotherapy and go straight to surgery if there is availability. But I think the challenge of the OR scheduling is becoming real, especially for elective procedures. And how do we define elective procedures, right? And also we have to shift balance there.

Brian Rini: Yeah. No, we're having the same sort of mental debate and God forbid some of the surgeons get infected and need to be quarantined and we have a whole other resource drain. And so we're having those same discussions. I'm not sure what the right answer is, but we're generally coming down on the side of doing it, as you say, in fit patients. Which is what we were doing anyway. But I've heard both sides of that debate.

Petros Grivas: I hear you. And we debate even ourselves whether we should have some kind of algorithm or guideline criteria in order to help individual providers make these decisions. And it's something we're working on internally and, of course, very detailed documentation about the patient discussion. And even with cases with prostate cancer, I know that some of the low-risk cases they postponed, and the intermediate-risk prostate cancer or high-risk prostate cancer, how urgent is this? Or after trial urothelial cancer cystectomies, the cancers also [inaudible 00:11:46] is a hard decision.

Let me talk a little bit about and ask you guys about the problem we have with no data, right? Because it's so quick, it happened the last few weeks. So they need to gather data and I think there is an initiative across different cancer centers. Brian, in your institution, Dr. Warner is leading an effort with a data instrument collection tool and we plan to participate in that. Could you comment a little bit about how we can generate real-time data? You are a leader in the field of research.

Brian Rini: Yeah. So Jeremy Warner here has set up a REDCap database basically for any cancer patient diagnosed with COVID infection just to gather data. Because as you say, there's just anecdotes flying around and people making decisions based on them, which is never good but unfortunately necessary now. But this is really just sort of a global attempt to get people to just enter a very simple REDCap form. Cancer patients who are admitted who have COVID infection and then what happens, how are they treated, what's going on with their malignancy; just all the data elements you might imagine. And so that hopefully as the days and weeks go by, that maybe we can have some more informed decisions.

I know we're trying to figure out a care path for how to handle these folks in the hospital who are usually older, have the obvious comorbidity of cancer, but often others. And does the algorithm for everybody else apply to them? And they might have cytopenias and so it just gets infinitely complex. So, as you say, we're in a data-free zone. And so we're trying to just collect some data and get some global experience, so that when the wave comes here or the second wave comes, or the next wave comes whenever, that at least we're a little better prepared.

Petros Grivas: Absolutely. I totally agree with you. There's an urgent need. Ali, you want to comment a little bit about the data instrument collection that we have been designing? And comment on how we can implement that in different centers?

Ali Khaki: Yeah, so as Dr. Rini mentioned, there's this new REDCap data collection tool that's been set up by Jeremy Warner. There's a huge cancer consortium of multiple institutions that has been assembled that have been working on this. Initially started on Twitter and moved to emails and now sort of we've formalized a process at multiple institutions. The Vanderbilt IRB had declared the project exempt at their institution, and other institutions are encouraged to work with either their IRBs to make sure they're permitted to enter data.

Though notably, we're not collecting any patient-identifying information on this. And so the perception of the Vanderbilt IRB, and similarly UW IRB, is that as long as no patient-identifying information is collected or saved anywhere, then this is something that can likely be IRB exempt. We're still going through the process at our institution, but the hope is that we can sort of begin to collect this data, and so we can have a bit more informed discussions and guidance for our patients. Right now the study that's being sent around by everyone about cancer patients is a study that's published in Lancet Oncology earlier this month that had 18 patients out of something just under 1600 patients with cancer. And showed that those patients did worse, but 18 patients are not what you want to be making your decisions off of.

Brian Rini: Yeah. And some of those patients, as I understand it, had cancer resection three years ago, so they wouldn't be what we would consider sort of "active cancers". So yeah, as you say, it's a relatively data-free zone. But I agree, that's the only data that I'm aware of.

Petros Grivas: That's right. And we tried to work with our IRBs to get this registry approved and up and running very quickly and I think it will be one of those situations where probably real-time emerging data might potentially help us make decisions. As we go through the next few...

In that context, if I may ask, Brian, with your experience in research all these years, in leadership, I know you have been thinking about clinical trials for COVID-19 in cancer patients with cancer and also without patients with cancer. Any particular sorts of come to mind for clinical trial design priorities? In specifically patients with cancer?

Brian Rini: There's a remdesivir trial that's a placebo-controlled trial, actually, that I think we're about to open next week. Tocilizumab, as you know, IL-6, is increased in these patients, and so there's some anecdotal use out of Italy of using that. So we're trying to see about either doing a trial or just developing a care path where we can get some experience. I've been involved with conversations about using convalescent plasma, which has actually a long history back to the Spanish flu. About taking plasma from patients who've recovered, which have, obviously, antibodies and then infusing them into patients with active infections.

So I think it's sort of an all hands on deck approach and I don't know that anybody really knows what works. I've again heard, not direct experience, that steroids do not seem to help. People are using things like Plaquenil®; I'm not really sure there's efficacy, I've not seen anything convincing. So I think the shorter answer is we don't know, but a lot of different mechanisms are being tried. And again, hopefully, these database efforts and some more experience, growing experience, can at least help us get rid of some things that aren't helping patients and focus on things that are.

Ali Khaki: Petros, I was excited to see today that New England Journal published its first randomized controlled trial in COVID-19 patients. Lopinavir/ritonavir trial just got published. Unfortunately, it was a negative trial, but I was impressed. They recruited 200 patients in just under a month from January 18th to February 3rd, and the results were published on March 18th. So that sort of turnaround, hopefully-

Brian Rini: That's amazing.

Ali Khaki: ... if we can do that with additional agents, we can find things that will work for our patients.

Petros Grivas: This was amazing. I saw that, and it tells you that when we really are in a crisis, as Brian mentioned before, you have to be creative and work under pressure to make things happen. So all the red tape around research that keeps us from progressing, I think could potentially be reduced after the COVID-19 crisis has settled.

Brian Rini: All a matter of motivation, right? Everybody's motivated, everybody's on the same page, we're all pulling in the same direction. And so it's a testament to what you can get done. And just the raw determination of the medical community. I don't think anybody gets involved in this industry without being sort of tough and determined. And so, again, hopefully, we'll get on the other side of this and be able to look back at some of these victories.

Petros Grivas: Absolutely, I agree. I think that it will. We'll become stronger at the end after we go through this. Let me close our discussions here, just to pick at your brains regarding mechanisms here. And we talked a little bit before about immune checkpoint inhibitors and whether these could increase our immune system and potentially do a good thing, or potentially releasing cytokine release syndrome and make it worse.

Or even the question about NSAIDs that came out from France a few days ago. Many of our patients with GU cancers are using those medications or ACE inhibitors. Of course, we don't have data, but do you have a sense of... And these are questions we're going to gather and collect with the registry we're creating, but any thoughts about these approaches? And you have a patient in the clinic, any particular discussion you would have with them?

Brian Rini: So we did a bit of a podcast over the weekend with Chuck Drake who was talking about some of the preclinical data. And it's one of those things where depending on what data you look at, either they're a good thing or a bad thing. And I'm not aware of clinical experience yet. But if you look at the preclinical models and their effects, it's that they're mostly PD-1, PD-L1 inhibition. And if I remember the take-home correctly, patients under the treatment of PD-L1 inhibition might have a harder time getting infected, but then they might have a hard time controlling that infection if they are infected.

And so again, this is all based on preclinical models, so none of it's human data. And so I think the real answer is we don't know. We obviously are using a ton of immunotherapy. I'm not aware of data yet that those patients are more susceptible to infection or have worse infections. But it's probably the tip of the iceberg. So I think if you ask in a week or two or a month, I think we're probably going to have a better handle on that.

Petros Grivas: I totally agree. Ali, any comments from that?

Ali Khaki: Yeah. Nothing else about the immune checkpoint inhibitors. I'd say about the NSAID stuff that's been going around, I've actually been pretty disappointed by the WHO making such a strong recommendation against NSAID use. I think that based off of preclinical data in this ACE2 model, I think it's irresponsible for us to sort of scare a population that's already scared and uncertain, off of such weak evidence.

I think that you could hypothesize why this could or could not work in different ways. And NSAIDs are something that's a widespread medication that has many uses, especially for people who are having a febrile illness. I think that you could nudge people to take acetaminophen before NSAIDs, but I think coming down so strongly against NSAIDs, I think we need to be careful to not perpetuate uncertainty at a time when there's so much already.

Petros Grivas: And I think this brings up the issue that we discussed before, in the data-free zone and how much data points can tip you and make a decision versus the other which is very, very difficult to, of course, predict. Any last comments from either Brian, we'll start with you. Any take-home messages from the folks in the audience regarding this crisis and specifically GU cancer, something to keep in mind?

Brian Rini: Ali, you want to go first?

Ali Khaki: Sure. I'd say that my plea would be for everyone to help us out with the cancer consortium, the COVID-19 cancer consortium. So we don't know much of anything right now and there's much we can learn and so we will learn by working together. And so please, if you are taking care of cancer patients, please consider working with your institution to help share some data so we can learn something about these patients in an expedited manner.

Brian Rini: Yeah, I agree. I was going to say keep the lines of communication open. Even anecdotes at this point might be helpful. And then obviously collecting data as mentioned, prospectively. And we have such great ways to communicate now, even compared to 10 years ago, that we just need to share in the experience and sort of learn from each other. And, unfortunately, learn from places that are experiencing the wave before us. So obviously in Seattle, you guys are ahead, so to speak, in terms of infection rate and such. And so cities like Nashville and others that are, fortunately, behind that hopefully can learn from some of the experiences. Even if it's about the allocation of beds and canceling elective surgeries.

And I think people are moving rapidly, and as cities sort of make decisions and hospitals make decisions, I think others are very soon to follow. And I think gone is the skepticism that this is a real problem. There was some of that early on, understandably, but I think that's sort of washed away. And so I think the leaders in the medical community, globally and nationally, are taking the lead and I think others are following.

But the take-home message is lines of communication open, and to patients as well. Patients should be talking with their doctors about if they really need to go in for that appointment, can they hold their medication. Just what are strategies to reduce risk, globally speaking.

Petros Grivas: I totally agree with both of you. I think that communication is essential, both between providers, scientists, and the patients, of course, should not be afraid to ask questions and they kind of work with their individual providers. We're trying to define what is elective, what needs to be addressed right away, what can wait. And these decisions, probably, we'll make case by case.

I would like to thank both of you for your time. I know you're super busy, and being available to discuss today was a privilege. So thank you so much, both of you. And hopefully, we'll be able to come back up maybe after a few weeks and see what progress we have made as a scientific community.

email news signup