Chemoradiation in Urothelial Carcinoma: The Herculean Effort Behind the SWOG 1806 Trial - Petros Grivas
April 29, 2021
Alicia Morgans speaks with Petros Grivas to discuss the intricacies of the SWOG 1806 clinical trial, led by Dr. Parminder Singh. This multi-institutional study aims to evaluate the efficacy of adding atezolizumab, an anti-PD-L1 agent, to chemoradiation treatment in patients with localized muscle-invasive urothelial carcinoma. Dr. Grivas emphasizes the collaborative nature of this "Herculean effort," involving multiple Cooperative Groups within the National Clinical Trials Network (NCTN). The study presents various chemoradiation options and aims to investigate patient-reported outcomes and biomarker data. Morgans highlights that the trial provides an excellent opportunity for more widespread adoption of bladder-sparing chemoradiation regimens, addressing a common misconception that such treatments are effective only in specific locations. Both Drs. Morgans and Grivas underscore the trial's patient-centric significance and urge for increased awareness and enrollment to bring it to fruition.
Biographies:
Petros Grivas, MD, PhD, Professor, Clinical Director of Genitourinary Cancers Program, University of Washington, Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center.
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts.
Biographies:
Petros Grivas, MD, PhD, Professor, Clinical Director of Genitourinary Cancers Program, University of Washington, Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center.
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts.
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ASCO 2021: Steps Toward a Bladder-Intact Cure for Muscle-Invasive Bladder Cancer
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Read the Full Video Transcript
Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist and Associate Professor of medicine at Northwestern University. I'm so excited to have you here with me today, a friend and colleague, Dr. Petros Grivas, who's an Associate Professor of Medicine and GU Medical Oncologist at the University of Washington, in Seattle. Thank you so much for being here with me today, Petros.
Petros Grivas: Thank you so much, Alicia, for having me. I'm very excited to discuss this with you.
Alicia Morgans: Wonderful. So I wanted to talk with you as we kind of review some of these really exciting clinical trials in urothelial carcinoma. The SWOG 1806 trial led by Dr. Parminder Singh, who is a fantastic advocate for these patients and really has worked across all of the cooperative groups to get engagement between SWOG, ECOG, and ALLIANCE to have this team come together for this trial of chemoradiation in patients who have localized muscle-invasive urothelial carcinoma. Can you tell us a little bit about it, please?
Petros Grivas: Absolutely. I would like to echo what you said, Alicia, this is a gigantic, Herculean effort, I can use this Greek word by Dr. Singh and many others. And I know you have been involved in the evaluation of patient-reported outcomes, and I had the opportunity and honor to be involved in the translational medicine efforts in this study. All the Cooperative Groups work together, and I think it's an example of how you can work together with different Cooperative Groups within the NCTN. The study, as you mentioned, the SWOG 1806, is led by SWOG, NRG, ECOG-ACRIN, and Alliance are also involved heavily in trying to answer the question, in patients who opt to go for bladder preservation, which means maximum TURBT, optimal TURBT followed by concurrent chemotherapy and radiation, does the addition of atezolizumab, an anti-PD-L1 agent, improve outcomes? So the design is very simple.
It's a randomized phase three study with again, a maximum TURBT followed by concurrent chemoradiation, or chemoradiation plus atezolizumab. And I think the importance of this study with the goal to improve upon outcomes in this disease, in terms of clinical complete response rate, event-free survival, and the prominent point is event-free survival is to illustrate whether there is some potential additive benefit or synergism with the addition of immunotherapy to the backbone of chemoradiation. The chemotherapy radiosensitizer, there are three options there, either cisplatin alone once a week or the 5FU and mitomycin-C regimen based on the BC2001 trial from Dr. Nicholas James in the UK, or gemcitabine alone. And either of those three options is available and I would say that the other key point is that because of the nature of the trial, there is no interim look when dealing with radiation.
People go through radiation therapy and they evaluate at the end of the chemoradiation with cystoscopy, possible TURBT, even cytology, and of course, CAT scans and labs in order to again evaluate the primary endpoint of event-free survival. There are, I would say, a number of secondary and exploratory endpoints, as I mentioned before, clinical complete response rates, overall survival, metastasis-free survival, bladder intact. Event-free survival is a key one, as I mentioned, the primary endpoint, and then we have the opportunity to work on patient-reported outcomes, and you are involved in that, and of course, [inaudible] biomarker data, and we actually have a call soon to evaluate that option, the trial is ongoing and it has accrued well. I think it's hugely important to raise awareness and accrual in this trial. It is great to have support from a lot of urology and oncology colleagues like Dr. Seth Lerner, and SWOG, and many others.
And of course, radiation oncology leaders like Jason Efstathiou at MGH and many others. Again, it's a huge army of people who worked hard on this study, and we look forward to having some results in the future, I think the trial seems again feasible, and I think with the support of all the team members, hopefully, we will get it through and we'll answer the question whether the addition of atezolizumab adds value or not in the backbone of chemoradiation in this bladder preservation approach. I just wanted to make a very, very quick point, Alicia, that Dr. Arjun Balar and others are working on a very similar trial with pembrolizumab. It's a very similar design, there are a few small differences here and there, but the backbone of the trial is similar, and this using pembrolizumab, it's another Keynote trial, and I think Dr. Balar is leading that effort, and I think both those trials will be important and answer this important question.
Alicia Morgans: I truly agree, and I also would emphasize for our community that I think it's a really good opportunity for those of us who are not commonly using a chemoradiation approach in appropriate patients to kind of dip our toe in this bladder-sparing water. I ended up training in Boston, so I have a lot of comfort around chemoradiation, but I've heard it said that chemoradiation, bladder-sparing only works in Boston or only works in select areas. I think what this trial is showing is that this type of approach actually can be deployed across multiple institutions, can be done successfully, and is a really good opportunity for patients to have the thought that they might be able to keep their bladder because it is a life-altering experience to lose one's bladder.
We all know that, and I think from a patient-centric perspective, this is a really, really important study, this and of course, Dr. Balar's study as well. So thank you so much for sharing your thoughts on this. We have put many patients actually on this trial, at least eight or 10, and we are trying to get more on all the time, and I know that you and your team are working on that too. Let's keep the accrual up, let's complete this trial, let's analyze the data, and let's find out, how can we do better and how can we be successful with a bladder-sparing approach? Thank you so much for your time.
Petros Grivas: Thank you so much, Alicia. I totally agree with you.
Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist and Associate Professor of medicine at Northwestern University. I'm so excited to have you here with me today, a friend and colleague, Dr. Petros Grivas, who's an Associate Professor of Medicine and GU Medical Oncologist at the University of Washington, in Seattle. Thank you so much for being here with me today, Petros.
Petros Grivas: Thank you so much, Alicia, for having me. I'm very excited to discuss this with you.
Alicia Morgans: Wonderful. So I wanted to talk with you as we kind of review some of these really exciting clinical trials in urothelial carcinoma. The SWOG 1806 trial led by Dr. Parminder Singh, who is a fantastic advocate for these patients and really has worked across all of the cooperative groups to get engagement between SWOG, ECOG, and ALLIANCE to have this team come together for this trial of chemoradiation in patients who have localized muscle-invasive urothelial carcinoma. Can you tell us a little bit about it, please?
Petros Grivas: Absolutely. I would like to echo what you said, Alicia, this is a gigantic, Herculean effort, I can use this Greek word by Dr. Singh and many others. And I know you have been involved in the evaluation of patient-reported outcomes, and I had the opportunity and honor to be involved in the translational medicine efforts in this study. All the Cooperative Groups work together, and I think it's an example of how you can work together with different Cooperative Groups within the NCTN. The study, as you mentioned, the SWOG 1806, is led by SWOG, NRG, ECOG-ACRIN, and Alliance are also involved heavily in trying to answer the question, in patients who opt to go for bladder preservation, which means maximum TURBT, optimal TURBT followed by concurrent chemotherapy and radiation, does the addition of atezolizumab, an anti-PD-L1 agent, improve outcomes? So the design is very simple.
It's a randomized phase three study with again, a maximum TURBT followed by concurrent chemoradiation, or chemoradiation plus atezolizumab. And I think the importance of this study with the goal to improve upon outcomes in this disease, in terms of clinical complete response rate, event-free survival, and the prominent point is event-free survival is to illustrate whether there is some potential additive benefit or synergism with the addition of immunotherapy to the backbone of chemoradiation. The chemotherapy radiosensitizer, there are three options there, either cisplatin alone once a week or the 5FU and mitomycin-C regimen based on the BC2001 trial from Dr. Nicholas James in the UK, or gemcitabine alone. And either of those three options is available and I would say that the other key point is that because of the nature of the trial, there is no interim look when dealing with radiation.
People go through radiation therapy and they evaluate at the end of the chemoradiation with cystoscopy, possible TURBT, even cytology, and of course, CAT scans and labs in order to again evaluate the primary endpoint of event-free survival. There are, I would say, a number of secondary and exploratory endpoints, as I mentioned before, clinical complete response rates, overall survival, metastasis-free survival, bladder intact. Event-free survival is a key one, as I mentioned, the primary endpoint, and then we have the opportunity to work on patient-reported outcomes, and you are involved in that, and of course, [inaudible] biomarker data, and we actually have a call soon to evaluate that option, the trial is ongoing and it has accrued well. I think it's hugely important to raise awareness and accrual in this trial. It is great to have support from a lot of urology and oncology colleagues like Dr. Seth Lerner, and SWOG, and many others.
And of course, radiation oncology leaders like Jason Efstathiou at MGH and many others. Again, it's a huge army of people who worked hard on this study, and we look forward to having some results in the future, I think the trial seems again feasible, and I think with the support of all the team members, hopefully, we will get it through and we'll answer the question whether the addition of atezolizumab adds value or not in the backbone of chemoradiation in this bladder preservation approach. I just wanted to make a very, very quick point, Alicia, that Dr. Arjun Balar and others are working on a very similar trial with pembrolizumab. It's a very similar design, there are a few small differences here and there, but the backbone of the trial is similar, and this using pembrolizumab, it's another Keynote trial, and I think Dr. Balar is leading that effort, and I think both those trials will be important and answer this important question.
Alicia Morgans: I truly agree, and I also would emphasize for our community that I think it's a really good opportunity for those of us who are not commonly using a chemoradiation approach in appropriate patients to kind of dip our toe in this bladder-sparing water. I ended up training in Boston, so I have a lot of comfort around chemoradiation, but I've heard it said that chemoradiation, bladder-sparing only works in Boston or only works in select areas. I think what this trial is showing is that this type of approach actually can be deployed across multiple institutions, can be done successfully, and is a really good opportunity for patients to have the thought that they might be able to keep their bladder because it is a life-altering experience to lose one's bladder.
We all know that, and I think from a patient-centric perspective, this is a really, really important study, this and of course, Dr. Balar's study as well. So thank you so much for sharing your thoughts on this. We have put many patients actually on this trial, at least eight or 10, and we are trying to get more on all the time, and I know that you and your team are working on that too. Let's keep the accrual up, let's complete this trial, let's analyze the data, and let's find out, how can we do better and how can we be successful with a bladder-sparing approach? Thank you so much for your time.
Petros Grivas: Thank you so much, Alicia. I totally agree with you.