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Zachary Klaassen: Hi, my name is Zach Klaassen. I’m a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I’m delighted to be joined on UroToday by Dr. Srikala Sridhar, who is a medical oncologist at the Princess Margaret Cancer Center in Toronto, Canada. Kala, thanks so much for joining us on UroToday.

Srikala Sridhar: Thanks for having me, Zach. I’m super excited to be here.

Zachary Klaassen: Awesome. We’re going to talk about a really interesting paper you guys recently published in Clinical Genitourinary Cancer, looking at just what’s going on with investigator-initiated trials and really industry-sponsored trials. And it’s a great analysis, and I’m looking forward to your slides and sharing for our audience. So maybe just pull those up, and we’ll roll through the background, methods, and results.

Srikala Sridhar: OK. So I am super excited to present the results of our study that we published, as you mentioned, in Clinical Genitourinary Cancer in 2024.

So this was really a comparison of industry-sponsored trials—so really trials that are led by the pharma industry—and investigator-initiated trials—those led by investigators, sometimes via cooperative groups—in advanced GU cancers in four countries: in the US, Canada, UK, and France. I should say here are my disclosures, and moving on.

So by way of background, we know that clinical trials are either industry-sponsored or investigator-initiated, really depending on the source of the funding. ISTs are usually run by pharmaceutical companies developing new drugs aimed at garnering regulatory approval. IITs are complementary to ISTs and are developed by academic investigators or cooperative groups, often sparked by clinical need. And the intent of these is often for publication or to secure further research funding. But I think both are really vital in advancing the field of oncology.

To date, there’s been very little published about current trends in ISTs or IITs in GU oncology. And so the aim of our study was really to assess these trends in four countries which have somewhat similar health care infrastructures.

We searched through clinicaltrials.gov for GU trials from January 2007 to December 2021, and we designated these ISTs or IITs largely based on the funding source. And we collected a number of details about these trials.

Overall, about 5,834 GU trials were identified, with a balanced distribution of ISTs—about 3,064 ISTs—and about 2,700, give or take, IITs. So about 52% and 47.4%, respectively. The US conducted the most GU trials, at just under 4,000, followed by Canada, France, and the UK.

In terms of the results, we found that most ISTs were phase 3 trials with over 500 participants. Most IITs, on the other hand, were open-label phase 2 studies with 20 to 49 participants—so usually smaller studies. From 2017 onwards, there was a shift towards more industry-sponsored studies. This was most noticeable in Canada and the UK.

And interestingly, we found that the COVID-19 pandemic did not really have a major impact on the growth of ISTs or IITs. But I can tell you, when we were doing these trials, it really impacted accrual because sometimes we weren’t seeing these patients in person, and I think that affected the trust that we built with patients. And getting them onto trials was harder.

If we look at some of the trends, you can see the IST, shown here in blue, had a steady growth across all four countries that we looked at, whereas IITs, shown in red, have lagged behind the ISTs and not shown as significant growth. And I think this is an important point.

So, really, in conclusion, we found the gap between ISTs and IITs continues to widen, likely driven in part by resource and funding challenges faced by investigators. And there are some barriers to completing IITs that really need to be better understood to promote IIT development and maintain their academically driven intentions.

So the key take-home message here: I think IITs are key to moving the field forwards. They are complementary to ISTs, and they often ask questions that are not necessarily asked or addressed by industry-sponsored trials. We need to ensure strong partnerships at every level—investigators, cooperative groups, industry, patient-advocacy groups—to really bring these trials home. And we need to support investigators with protocol development, trial conduct, and funding. And having done a number of investigator-initiated trials myself, I think this is really, really critical to ensure that these trials get done and published. So thank you.

Zachary Klaassen: Awesome presentation. Just some really important data. And I think a wide range—you guys collected almost 15 years of data. One of the things, I think, just as a key home message: why is it important to have patients accruing to both phase 2 or even phase 3 IITs, but also to the big ISTs trials? I mean, we’re getting almost different answers from each of these. So how would you explain the importance for both of these trial designs?

Srikala Sridhar: Yeah, I think they’re both absolutely critical. When we think about the industry-sponsored trials, these are often very large trials. They’re asking big, important questions. They’re looking for overall survival advantages, and they really have the resources to bring these trials to completion and even publish them. And so those are two really important points that these trials then can really change the face of how we treat our patients today.

We’ve seen big trials, for example, in urothelial cancer front line. We’ve seen the EV-302 study that took EV, which is enfortumab vedotin, plus pembrolizumab, and that was compared against standard platinum-based chemotherapy and showed a very significant improvement in overall survival, just updated at GU ASCO this year. And that has changed our frontline treatment in urothelial cancer for the first time in decades. We’ve not seen this. So I think these industry-sponsored trials are critical and important and ask these big questions, multicenter, and really rigorously done in many cases. So industry-sponsored trials are important for those reasons.

I think, at the same time, the investigator-initiated trials are important because sometimes they’re asking questions that are not asked by the industry-sponsored trial, or they’re looking at other things, like some of the correlative studies, some of the quality of life. And sometimes we can do smaller phase 2 studies that then inform the phase 3 trial design. So that’s an important role for investigator-initiated studies.

Other times they’re tumors that are more rare or cancers that are more rare. I mean, I certainly have a trial in penile cancer. And I can tell you it’s been a struggle because it’s a rare cancer, but it was even a struggle to get the study underway because people are going, “Why penile cancer? Where’s the relevance? How many patients get this cancer?” But I think as investigators, as clinicians, we see the need for these trials, and we really need these to move forward. But I think, at the same time, we need to be ensuring that we’re asking the right questions, that we have quality in what we do.

That maybe we’re better at doing really solid, deep phase 2 studies that are not huge, but are asking really good questions, and importantly, are following up on patients properly, that we know what’s happening to all patients, that they’re not being lost to follow-up. I mean, we know, for example, in the VESPER trial—again, I think it’s a great idea that everything was really good. However, a number of patients—almost 30%—were lost to follow-up. And I think that’s an important consideration.

Zachary Klaassen: Yeah, great points. And I think probably the ultimate IIT is STAMPEDE. But I think one of my favorite trials is the POUT trial. And that’s a hard trial to probably get industry sponsorship, but literally a practice-changing trial when that was published, I believe in 2018. So you’re right. I think it’s complementing each other. It’s not one versus the other, right?

Srikala Sridhar: Yeah, absolutely. And I think along the same lines of POUT, we also had the CHAARTED study, which really—sometimes it takes drugs that are off-patent and looking for ways to use them that could still be beneficial, where maybe the company is no longer interested in the drug because it is off-patent. So POUT is that kind of study, CHAARTED is kind of that study.

And you brought up earlier the STAMPEDE study, which is a really interesting multi-arm, multi-stage trial that was very agile and able to move and change arms and add arms. And I think that was really, really clever as a large trial. And then we’ve also got trials where it’s multi organizations. Many people are involved just to say that we can do it. And that’s similar to the TIGER trial as well—that is a huge collaboration across, again, multiple groups and funding from many different places, including things like Movember. So I think that it’s really important to look at these trials because they’re all very unique in their own way.

Zachary Klaassen: Yeah, absolutely. Reading your paper, I noted that you said that there was more reporting of data in publications for ISTs versus IITs. Is that because it’s phase 3 versus mostly phase 2, or is there other reasons behind that, you think?

Srikala Sridhar: That’s a great question. I think we don’t know exactly why that is. But I think one thing—when we do trials, it’s really important that we have robust data collection, that we’re able to write these trials up, that we’re able to analyze the studies. The statistics are important. And so I think you need that part in order that these trials actually are published. And even if they’re negative, I think sometimes the industry-sponsored trials—maybe they do a better job at getting the data out there, whether they have people who help write the papers or what have you, but they just make sure that it gets out there, whereas it’s harder because so much is on the investigator who’s running these trials to write these trials up. But I know from having done them myself that you’re sitting there at 1:00 AM writing these trials up.

Zachary Klaassen: Yeah, exactly. Negative follow-up. Yeah, exactly, exactly. At the last few years of your study, there was more of a widening between ISTs and IITs. And so I think in your discussion, you mentioned some of the reasons, even aside from funding—which is more difficult to get for IITs in the last several years. Is there other infrastructure things we can look at to try to improve not just opening these trials, but also completing these IITs?

Srikala Sridhar: Yeah, I think that’s a great question. So I think that one of the things that’s really critical—and it’s critical, I think, across the field of oncology—is really this need for this multidisciplinary collaboration but also multi-organizational collaboration, right? So from the investigator to cooperative groups, if you’re using that mechanism, to industry. And then we need the patient advocacy groups also involved, like, say, for example, the Movember example, where they supported those kind of studies. I think that’s important.

We also need collaboration at the science level—our preclinical scientists. I think everybody really needs to be working together. That’s going to be important to start. I think we really need to place an emphasis on good quality, good study design, really good endpoints. I think we need support and infrastructure to create these trials that are going to answer the questions that we’re asking. That’s going to be really, really important.

And we need mechanisms to follow up on these patients, so they’re not lost to follow-up, for example, or we understand the impact of subsequent treatments. And I think all of that needs that really dedicated trial infrastructure because many of us who’ve done investigator-initiated trials—we write the protocol, we look for funding. I almost want to think that it would be nice if some of our industry partners would have a little offshoot that’s really solely dedicated to investigator-initiated trials. And some of them have nice platforms in which you put your idea in, it gets evaluated, and it gets turned around quickly because timing is another thing.

I know in one of my trials, we just spent a lot of time trying to get the trial off the ground, and then once it was off the ground, there’s been a long time accrual. So I think that time frame needs to be quick because the field is moving so quickly right now that if you don’t move quickly, the question may not still be relevant.

Zachary Klaassen: Yeah, absolutely. And I think you mentioned a good point—some of these industry partners will have IIT divisions, and that may be harder to capture in a study like this. But I think it’s important that if somebody does have a good idea and they’re using a drug or an intervention, that they may be able to partner with industry as well, even from an IIT standpoint. I know you gave us some great take-home messages at the end of your slides. Maybe just a final thought or two to conclude our discussion?

Srikala Sridhar: I think the big thing is, I think that investigator-initiated studies remain important and remain complementary. I mean, these are going to impact us in the clinic, even asking questions such as—what about de-escalation of treatment? How do we do that? Can we do that? Those are going to be really important questions that maybe other people aren’t so interested in, or industry may not be that interested in answering those questions.

So I think we really need to do everything we can to support not only the investigator but also the concept, the conduct, and the ultimate follow-up and writing up of these investigator-initiated trials. I think we need to think about how we do that, and we need to think about novel models of trial design in the setting of investigator-initiated trials. And hopefully that will lead to more of these happening in the future.

Zachary Klaassen: Absolutely. Kala, congratulations on the great work, and thank you, as always, for joining us on UroToday to share your experience.

Srikala Sridhar: Absolutely. Thanks so much for having me. Take care.