Phase 2 TIDE-A Study: Thoughts and Potential Treatment Impacts

A roundtable discussion, moderated by Brian Rini, MD, addressed considerations for clear versus nonclear cell kidney cancer, as well as recent data from ESMO 2023. Dr. Rini was joined by Tian Zhang, MD; David McDermott, MD; and Hans Hammers, MD.

In the next segment of the roundtable series, the panel shared thoughts on the TIDE-A study and best practices for starting and stopping TKI therapy in RCC patients.

Watch the next segment in this series.

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Dr. Rini: One more bit of ESMO data to talk about. There was a study called TIDE-A out of the Italian group. It was axitinib/avelumab upfront I think for 9 or 12 months, and then patients who were not progressing, were stable disease or better I believe, could stop the TKI [tyrosine kinase inhibitor], got scanned I think every 2 months, and then when they progressed, they went back on. It was one of the first formal intermittent approaches to TKI. We all agree that chronic TKIs wear people out. We just keep giving them and giving them and giving them, and that’s probably not the right strategy, at least for most patients. Any thoughts on either that study, the data, and I feel like there’s a lot of data we didn’t see in the presentation, or just the approach in general? Tian, do you want to start?

Dr. Zhang: We do this in our clinics for on-label use; we stop and start based on tolerability. But this was a very careful analysis, and they had specific requirements for holding. I think it’s a good approach, and it helps us say this is not an inferior way to help manage it, particularly later on.

Dr. Rini: David, what do you think?

Dr. McDermott: For the fourth time, I agree with Tian, but just adding on what she said, I think they should be given a lot of credit for doing this study because we need prospective data. Stopping TKI, I’m all about it. Go ahead.

Dr. Rini: You’re about not even starting it.

Dr. McDermott: There’s that too. But the other thing they did, and I believe this is true, is that they stopped for responders.

Dr. Rini: It wasn’t just stable disease, it was PR [partial response] or I guess CR [complete response].

Dr. McDermott: Right and that’s the right way to do this for all drugs in this class. This is one of the first studies I’ve seen that was not based on a time stopping, but a response stopping, but the 1 thing that I was not so pleased with is they were looking at just 8 weeks outcomes. Essentially, they were congratulating themselves for not seeing PFS at 8 weeks. I’m like, “Let’s do another scan; let’s get a little bit longer-term follow up.” Because what you’d like to see with VEGF TKIs is the VEGF is adding to the IO [immunotherapy] effect, which would allow you to stop the TKI for longer. I don’t think the study showed that, although there is a small tail on their PFS there.

Dr. Rini: We’ll see. I think about a quarter progressed at the first scan and maybe a quarter at the second scan, but if the other half was much more durable, we would agree that would be really meaningful. But we just don’t know yet.

Dr. McDermott: Correct.

Dr. Rini: But again, I think it’s important for doing this study. Hans, anything to add too?

Dr. Hammers: Bravo, Dr. [Roberto] Iacovelli. I think a fantastic study. I think it just fits in the notion to just use VEGF TKIS when you need them. The truth is when you’re doing really well on these combinations, at some point you need to lift the Band-Aid off the VEGF inhibitor. I think most of us, if we use IO/TKIs, I tend to stop brutally the TKI after 2 years if somebody has done well to see if it’s actually still needed. Quite frankly, maybe even earlier if they have toxicities. They really don’t end anything I think long-term. The most important question is did the patient have immunotherapy response or not? Lift it early. You may also mask a mixed response where actually you can spot the stereotactic radiation or surgery even with curative intent earlier. It just takes a lot of options away in optimally managing patients. Bravo lifting the TKI. You need to do that more.

Dr. Rini: Lifting the Band-Aid. Yeah, I tend to, and I borrowed this phrase from you Hans, be a big TKI interrupter. As patients get farther, everybody takes breaks. But then I’m like, “Take a week off. Going to Europe? Take a month off.” Myself and the patient become much more comfortable that they’re not clinging to this TKI response, like many patients are early, and they need it. It’s back to our initial discussion.

Dr. McDermott: Right, but you just mentioned a big part of it is getting the patient’s comfort level with holding treatment.

Dr. Rini: It takes a while to convince patients, but once you do and they take breaks, they come back and they say, and usually their significant other sitting next to them says, “Thank you, doc. Thank you for giving us permission to take a break.”

Dr. Hammers: Absolutely. Patients will be grateful to learn that lesson and they have to learn it. Some patients are really clinging onto them. I totally agree with you, but Thanksgiving is coming up, so anybody out there.

Dr. Rini: I’ll say take a break around life events, holidays, trips, all that. From a quality of life perspective, we’re not measuring this, but if you’re not on a drug, your quality of life is better. You don’t need a questionnaire to tell you that.