Ashish Kamat: Hello everybody and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, thoracic oncologist in Houston, Texas, and it's a pleasure to welcome to our forum, someone who's been here many times, doesn't really need an introduction. Dr. Apolo from the NCI NIH in Bethesda. We recently concluded a very, very interesting session at the BCAN think tank in Washington, DC. And Andrea, you led the discussion on the panel. There were several panels, of course, but you were sort of guiding the discussion on what have we learned from the different clinical trials, the trials, the tribulations, everything that goes with it.

So we'd love to hear what you have to say about your experience, also the panel's experience, and where is the community looking when we look back to learn from others' experience, and what can some of the younger folks listening in learn from yours and other mentors experiences as well?

Andrea Apolo: Well, first of all, thank you for having me. It's great to be here. And the BCAN think tank is really such a great meeting to do these kinds of panels where we learn from past experiences. And that was kind of the theme of this panel was if I could do it all over again, what would I do differently in my clinical trial? Lessons learned from bladder cancer clinical trials.

And it was really fun because we had a vast array of different expertise and multidisciplinary folks on the panel from surgeons running surgical trials to medical oncologists, running medical oncology trials, to multidisciplinary folks really running trials that included radiation, included surgery, included chemotherapy, immunotherapy. We had patient advocate on the panel, so that was really great in order to get their perspectives and how important it is to incorporate their thoughts early on into the design of clinical trials.

So we went from what are pearls that people can take with them? We really focused on cooperative group trials, but it applies to investigator initiated trials, trials that folks are designing and just how to... A lot of folks went through the timeline of how long things took, but what they came away with from at every step of the way. And we broke it down by everybody gave a talk, really focusing on their perspective of the clinical trial. So I started it and I talked on the AMBASSADOR clinical trial. And just to give a little background, it's a trial of adjuvant immunotherapy, pembrolizumab, patients with muscle invasive urothelial carcinoma. And I talked about managing a cooperative group study in a rapidly evolving treatment landscape.

And that's important because when we started off, immunotherapy was not being given in the muscle invasive setting. It was only really being given in the metastatic setting. And then another company was running a similar trial, two other companies were running similar trials, and then one of the drugs became FDA approved in the same indication that I was running within the clinical trial. So literally the landscape was changing as you're running the clinical trial and what do you do about that? How do you manage that? Especially how long it takes from the time you have a concept to opening up the trial and then enrolling within the trial.

Ashish Kamat: One of the things that struck me when you and others were talking was clearly the timeline that it takes, right? These trials take a long time, Andrea, and some of the folks listening in right now are clearly those that are starting their careers in oncology.

So what would you tell someone that is looking to either do it through investigator-initiated study or corporate group, or obviously pharma sponsored is different, but something that's coming from within, from you. What is your advice for them based on your experience with A, the timeline and B, the frustrations, which is frustrating for the investigator, but great for patients when newer drugs get approved that come in and encroach on your space?

Andrea Apolo: Yeah, I think that as an investigator, you're not trying to test a new drug for that particular tumor type in the regular way that the company is going to do that. So there has to be something very unique about what you're doing that the pharmaceutical company is not going to do. It's a question that as an investigator you have... So you have to pose a question that I wouldn't say is timeless, but will stand the test of time. And even if the landscape evolves, as it will, it just will, the question is still important and it still is very informative and you can build on it potentially.

So it doesn't have to be, not only does drug A work, but does drug A work in a particular setting, in a particular patient population under these conditions, maybe with a biomarker? Something very specific that will, although the landscape may change, which happened to me, it's still a very important study because for example, the AMBASSADOR study tested adjuvant pembrolizumab. The trial was positive for disease-free survival, and now it's part of the NCCN guidelines in addition to the other drug, nivolumab, which already had been already in the NCCN guidelines. So it added another option. And then it's building on that.

So other drugs are being tested in the setting now in combination with pembrolizumab, and we will know the effects of pembrolizumab by itself because we have this data available. So it's a very useful data set already. So when you're building your trial, building it with a unique question that your trial will answer, and it will help beyond the timeline of the trial, and not only just the drug, but also just the question specific to the population you're asking. So that's a pearl from my talk.

Ashish Kamat: Yeah, no, exactly. And I like the way you also said that, hey, because you're a part of a cooperative group or because you did this through a cooperative setting, it also had certain benefits, but also certain challenges. And when people are looking at our corporate groups from the outside, it almost looks like this non-transparent, nefarious sort of group of people that are just patting each other on the back. But when you actually get involved, you realize that they're actually patting the other person on the back trying to promote the careers of people and trying to actually get people to rise. It's not just self-congratulation.

So any advice to folks that are looking at corporate groups? I know you would say yes, join one, but any pearls of advice as to how you should do it, how one should approach it at different stages of their career?

Andrea Apolo: Absolutely. I think to me as a young investigator, when I was first starting out straight out of fellowship, being part of a cooperative group really led to mentorship. It led to a lot of networking. It exposed me to the ideas that people at a much more senior level than myself were asking at that point in the field and how they were approaching it statistically, strategically, with biomarkers, like all these different strategies that they were using. And I learned a little bit from everybody that then I can apply to the clinical trial that I was designing.

One of the other speakers was Dr. Hoffman-Censits from Hopkins, and she spoke on leadership and career opportunities in cooperative group trials. She specifically focused on her upper tract trial that she had or has, and she said that it let her open so many other doors for her within this group of physicians that treat upper tract, this rare tumor subtype. And she was able to participate in guidelines developments for upper tract, and it really opened up a lot of doors for her as a young investigator when she was designing the study and all of the trial is still ongoing. A lot of things kind of, because you get to work with a lot of folks that are working on similar areas, you really get to build on the work and then create other projects from that.

Ashish Kamat: And we can't do any of this alone. We have to do it together. It's sort of like teamwork, and not just the corporate groups, but even organizations such as BCAN. It gets people together. You get patient advocates, they come together and BCAN does a great job with North America and of course through the IBCG, we do things globally as well.

And by the way, congratulations, you're now an official member of the International Bladder Cancer Group. But if you look at international work, if you look at work in North America, if you look at the trials that are being done, many of them are local, some are global. Our audience at UroToday is global. Any pearls of wisdom from your essentially experience as to how people can approach multinational studies?

Andrea Apolo: Yeah, that's a lot more difficult and a lot of these multinational trials are not often done by the cooperative groups. They're often done through the pharmaceutical companies, although there are investigative trials that are supported by pharmaceutical companies that then become global. And you have to really understand what the landscape is within that country or countries where this is available. And then look at the opportunities and educational opportunities too.

For example, Dr. Lerner gave a really nice talk on how I build this, and then he talked about building and developing the lymphadenectomy study and how he negotiated this with multiple different parties. There had to be a standard of care in terms of doing the lymph node dissection in order to do an extended lymph node dissection, what exactly that definition is and how that was kind of a new concept to do a kind of surgical trial within the cooperative groups. And how he established, because there were different definitions of what a standard was, he kind of established a standard of what the minimum for a standard lymph node dissection would be, and then kind of what the extent would be for the clinical trial.

Also, Dr. Svatek also gave his talk on the journey through the cooperative group, mentorship, international relationships. He talked about, in patient advocacy, he talked about the BCG, all these different BCG strains that were available internationally to use for his study where he was testing BCG in patients with non-muscle invasive bladder cancer for the SWOG 1602 study. And he just said that it was very interesting and very helpful to be a junior faculty and to have the mentorship of the senior leadership in the cooperative group helping him in negotiating, using a lot of the agents that were used for the trial and how he wouldn't have gotten that kind of mentorship if it wasn't through the cooperative group. So that was very interesting lessons learned from running a cooperative group internationally.

Ashish Kamat: Yeah, no, I mean there's so many nuggets from the panel that you led. I mean, we could spend an hour on that, but clearly we don't. In closing, any sort of top three pearls you want to share with the audience as to clinical trials, cooperative groups, think tank? Anything, Andrea?

Andrea Apolo: I did want to mention also another talk that was given by the patient advocate was really important where the patient advocate really talked about engaging the patient early. He talked about, first of all, his experience of being a patient in a clinical trial, and then he talked about helping investigators develop clinical trials. So I think it's important to have the patient's perspective as to what it would be like to participate in this trial and what would make it easier for them to participate in this clinical trial and how to get the word out there. So once you build it, they have to come, right? So you have to build it in a way that makes it attractive to the patients that are participating in the study.

So involving a patient advocate is very important. So just to finalize, to wrap it all together... And then before I forget, one of the other concepts was there's a lot of sub-studies that come from these clinical trials. These are huge with a lot of patient samples. So there's all of these correlative and translational studies that can be done subsequent to the main data. So even if the trial was negative, you still have this wealth of knowledge and these samples that are so precious that you can do translational studies on. So a lot of great things for conducting these clinical trials.

So basically networking is very important. Leadership, not only learning from the leadership, but then becoming a leader and mentoring young faculty to then lead their own clinical trials is also very important. I mean, so many different profiles, I can't even prioritize them. I think everybody was so passionate when they were going through the panel about their own clinical trial and their own experience and everything that they got out of it, there was just so many different things that came out of the clinical trial or developing the clinical trial and executing the clinical trial for each investigator.

Ashish Kamat: Yeah, I think the underlying team was essentially mentoring, coaching, sponsoring, and then paying it forward. I think that was really very evident when it came to the cooperative group of pearls and wisdom. Andrea, thank you so much for taking the time. It's always a pleasure to chat with you. I know how busy you are, but really appreciate it.

Andrea Apolo: Well, thanks for having me. I really enjoy meeting with you and thanks for highlighting this panel. It was really fun to do and participate in, and I learned a lot. So I think that there's a lot to be learned. And we're actually talking about writing a manuscript because it's important to put this into some kind of written document that then a young investigator can use where, like a how to afford clinical trials for young investigators and lessons learned that others can learn from.

Ashish Kamat: Once the manuscript is out, we'll have you back here.

Andrea Apolo: Sounds great.

Ashish Kamat: Take care. Bye.

Andrea Apolo: All right. Bye.