The COVID-19 and Cancer Consortium: Understanding the Effects of COVID-19 on Patients with GU Cancers - Petros Grivas

Recorded Date: July 26, 2020

Petros Grivas, MD, PhD, joins Alicia Morgans to describe the work of the COVID-19 and Cancer Consortium (CCC19), a group of 100 institutions spanning the United States, Canada and Spain which has aimed to use "crowdsourcing" to collect data on how COVID-19 is impacting cancer patients. Dr. Grivas reviews a recent publication that found that the thirty-day mortality rate for patients with COVID-19 and cancer was 13%, more than double the rate of those without cancer. Dr. Grivas also discusses data depicting how specific antiviral medications tested in the COVID-19 pandemic fare in cancer patients such as hydroxychloroquine and remdesivir. Despite limitations in the data sets, overall trends suggest that hydroxychloroquine does not help but with remdesivir there is a benefit of lower mortality. Dr. Grivas also stresses the importance of still seeking cancer care or tests for diagnosis if suspicious symptoms arise even as the COVID-19 pandemic continues.


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.

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

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Alicia Morgans: Hi, this is Alicia Morgans, GU medical oncologist and associate professor of medicine at Northwestern University. And I am so excited to have here with me today, a good friend and colleague, Dr. Petros Grivas, who is an associate professor of medicine and a GU medical oncologist at the University of Washington in Seattle. Thank you so much for joining us here today, Dr. Grivas.

Petros Grivas: Thank you so much, Alicia, for having me and congratulations on your great work setting these interviews up.

Alicia Morgans: Thank you. Thank you very much. I think that it's been such a need for us as a community to have some outlets to discuss COVID-19 and the pandemic that is really afflicting all of our medical oncology, urology practices and other practices as we are trying to care for our patients with GU malignancies. And I know that you have done a lot of work in terms of trying to better characterize the disease and better understand the outcomes in your patients. And you've worked through a consortium, the CCC19 Consortium and have a recently published article that I would love to hear about.

Petros Grivas: Thank you, Alicia. Indeed COVID-19 has sent our lives in many ways and many colleagues of mine and myself would try to come up with this rapid way to get answers in our clinical practice. And through this quest of knowledge and quest of new data, we formed the COVID-19 and Cancer Consortium, so-called CCC19. I will urge the audience to look up in the website we have in CCC19, as well as in social media, Twitter, and others. And if possible, join this consortium that now has more than 100 institutions from multiple parts of the United States across the country, Canada, Spain and we're in active collaborations with ESMO, the European Society of Medical Oncology. Actually the ESMO president, Dr. Peters is one of the 11 steering committee members for CCC19 and I'm honored to be one of those 11 myself along with other esteemed colleagues.

Through that effort, we try to use this method of crowdsourcing as we call it, where we sent a survey through a red cap secure system to collect data in different institutions and the providers of patients who have cancers. And we can collect multiple data sets at the same time. And we have a central way to analyze the data statistically with statistician experts. And through that really, really amazing teamwork and collective efforts were able to publish the first manuscript in Lancet on May 28, 2020, just a couple of months after we formed the consortium. At that time, we had a little bit less than 1,000 patients. And as I always say, I wish we had zero patients, but sadly we all know that we're going to have many patients and many more patients in the database.

The main take-home points from the Lancet paper was that COVID-19 30-day mortality was about 13%, which is more than double of what you see in other data sets in patients without cancer. Definitely, cancer seems to be a risk factor for mortality. And there were some specific other risk factors like male gender or their age, poor performance status, the presence of cancer versus no evidence of cancer, as well as progressive disease. And we tried to get a little bit more granular after we published the paper in Lancet, which is by Dr. Kuderer and colleagues. And in the second paper that was just published just a few days ago. I think it was July 22nd in Cancer Discovery, our team with Dr. Rivera and Dr. Warner and others, including myself, would try to answer questions regarding the outcome of patients with cancer and COVID-19 in relationship with particular antiviral medications or other medications that can be given to treat COVID-19.

And one of the questions was about hydroxychloroquine. As we know, there's significant question out there in different studies. And so far, based on the scientific literature data hydroxychloroquine has not shown to be beneficial in COVID-19. And in our particular study, we look at using propensity score matching, we look at hydroxychloroquine in combination with other medications and this combination of hydroxychloroquine with other meds actually was associated with higher mortality at 30 days, higher risk of death at 30 days. You may argue here that you may have confounding biases and confounding by severity because the patients were very severe in terms of the disease, had more severe COVID-19, could potentially be more likely to get this medication, and also to die. So it's hard to know and we cannot comment on the causation here, but there was an association that aligns with other data sets that the hydroxychloroquine does not appear to help those patients with COVID-19 and cancer.

We also look at remdesivir. We all know that a clinical trial that looked at that antiviral medication in other patients. In our dataset, again, with all the caveats and biases of a prospective study, remdesivir alone was associated with decrease, with lower 30-day mortality in comparison with other therapies and had a trend towards the same thing, which means lower mortality when it was compared to no treatment at all. However, this second comparison did not reach statistical significance. If anything, there seems to be a trend of benefit with remdesivir, as in terms of lower mortality. And of course, with higher number of sample size, we may be able to draw more definitive results in the future.

Interestingly, there was the data from the recovery trial with high dose steroids in patients in the United Kingdom with COVID-19 that dexamethasone, it was able to reduce mortality, lower mortality in face of COVID-19 compared to best supportive care. In our database, again, we may have here confounding factors by indication and severity, but high dose steroids alone, by themselves, were numerically, but not significantly shared with actually higher mortality compared to no treatment. And when steroids, high dose steroids, were combined with other medications, other treatments, there was actually statistical significant higher risk of death that was contrary to what we expect. Obviously again, people who have more severe COVID-19 disease could be confounded and have a higher chance to die for other reasons.

We're moving forward with more data and we're actually trying hard to capture as much data as we can. The data analysis in the Cancer Discovery paper included about 2,186 patients, but we continue to capture more. In the future, we'll be able to provide more data and more analysis to inform this dialogue and the hypothesis-generating data in this devastating pandemic.

Alicia Morgans: 
I thank you for that recap. And also of course, for your work and for the work of the CCC19 team, all of the institutions that participate and really just want to emphasize that as we take care of our patients, as we think about ourselves and our own families, it is critically important that we rely on data. Data that is verified and data that we can trust, as we're choosing different treatments to try to improve outcomes for our patients. And I think at this point, thankfully, we are moving into a time when we have more data and can make those more educated guesses rather than simply making these guesses based on other, not as reliable sources. And unfortunately, now we have quite a bit of data as you report from CCC19 and other sources to help guide us in that decision making.

I would also note that we should all be on the lookout for more publications from CCC19. Certainly, there is a prostate cancer interest group that will be publishing data at some point, hopefully in the near future, as well as a cardio-oncology group, that's working on these things. There are multiple other groups that will publish on things that are of interest, I'm sure, to the GU oncology group who listens to this. And of course, the CCC19 overall team, the executive team like yourself and others will continue to update us as you continue to get data. I so thank you for this update. And I wonder as we close, what are your overall thoughts or a summary to lend to folks as they're thinking about this data?

Petros Grivas:
Thank you, Alicia, for the very important comments. I totally agree with you with everything you said. And I really, I have to give kudos to the whole team and Dr. Jeremy Warner, he's the captain, as we call him in Vanderbilt who is doing great work. And all the steering committee members are working hard in that direction. I think one of the take-home points for me to the community oncologist, academic oncologist and the patients is that we're all very worried about COVID-19. There's no doubt about it. And we do everything we can to help the patients and prevent spread. All the social distancing measures are very important. Obviously wearing masks, washing our hands, avoiding touching our face, and keeping social distancing is key.

At the same time, cancer does not go away. Cancer is not eliminated in the area of COVID-19. To the contrary, I'm personally very worried, Alicia, that delays in diagnosis and workup of suspicious symptoms, delays in screening tests as well as appropriate necessary therapies could have a toll on patients with cancer. My take-home point is, do not ignore cancer. Use the necessary precautions, be extra vigilant, but if a patient needs a workup and treatment for cancer, these should not be delayed. And we have published some data in the Lancet paper suggesting that, with all the caveats of the prospective data that the receipt of chemotherapy recently was not associated with worse outcomes with COVID-19. Despite the limited data, still makes me feel a little bit more comfortable practicing what I preach is when a patient needs workup and treatment for cancer, we should not delay that and we should move forward with all the precautions.

Alicia Morgans: That's an excellent message to everyone, particularly as we hope that we are in some lull in COVID-19 cases in some parts of the country, at least. That workup, diagnosis, initiation of treatment for patients who have cancer should absolutely be happening and should not be stopped because of a COVID-19 pandemic, because it's very possible that in the fall we could see a resurgence and we won't necessarily have the opportunity at that time to so easily continue that workup, diagnosis, and treatment. Cancer, as you said, does not go away and we need to balance the risks and the benefits of understanding what's going on in a patient while we also try to prevent, certainly, the infection by the SARS-CoV-2 virus and the development of COVID-19. But I sincerely appreciate your work, your efforts, and your message as we all try to grapple with this pandemic. Thank you so much.

Petros Grivas: Thank you so much, Alicia.