So Shilpa, you were part of the group that led this. Thanks for taking the time, and share with us your thoughts.
Shilpa Gupta: Thank you, Ashish, for the opportunity, and congratulations again for the highly successful meeting that we had a few weeks ago. So as you said, this is a topic that we all struggle with in our clinics and when we are treating patients on trials, the toxicity of systemic therapies related to bladder, so the local toxicities. And now that we have so many systemic therapies with different mechanism of action, we really don't know how to capture accurately what these drugs are doing. So this was one of the topics, as you know, when we were planning the meeting. One was the biomarker topic, the big umbrella, and one was toxicities. And in this toxicity there was a whole lot of different systemic blood toxicities, intravascular agent toxicities. And then there was also the PROs. And I was fortunate to be on the team that led the systemic therapy related toxicity.
So first I'll start with why we needed this because the CTCAE terms are too generic and events get misclassified and there's no organ and mechanism specific term for phenomenon like the immune related side effects. And as you know, most of these trials, even for metastatic disease, it gets coded as UTI or cystitis, just very generic, and we really don't know what's happening in the true sense. And I think it sometimes underplays the toxicities from some of these systemic therapies.
And the other drawback of the CTCAE is that the severity threshold hinges on interventions and not really the symptom burden. And you, Ashish, when you developed that while preparing for the meeting, like how to grade these, we were going back and forth, right? Because persistent debilitating bladder symptoms are still classified as low grade when they actually may not be low grade, if they're bothering the patient every day, even long term. Because if there is no actual intervention like a cystoscopy or an OR time, they just remain low grade, which I think is misclassification of some of these nagging toxicities. And we don't truly understand the morbidity of these agents. And again, trials with these systemic therapies report urinary adverse events, but they're all like a blanket term of hematuria, dysuria or UTI. So we really don't understand how to deal with persistent irritative symptoms.
So the team that we had to tackle this topic was co-led by myself, Dr. Noah Hahn from Johns Hopkins, and Dr. Andrea Necchi from Milan. And we met and we addressed the unmet need of a robust AE grading system to actually capture systemic drug-related bladder toxicities. And initially we wanted it to be just for immunotherapy, but we do understand there's other systemic agents like ADCs out there. So for the purposes of this meeting, we focused on the ICI-related bladder-specific toxicities, but this can always evolve with ADCs and other drugs. And then we developed questions for voting by the IBCG members, like the pre-voting. And then after the meeting we did a post-voting as well to see if we reached consensus. Which hopefully will come out in a manuscript later.
So this is pretty much the process and happy to answer any questions that you have. But this was the work that went into it, and while we can't share the specific statements here, that will be certainly disclosed in a paper.
Ashish Kamat: So thanks, Shilpa. And of course you are part of the scientific advisory board and a key member of the IBCG. So you were very instrumental in selecting the topics and of course leading the team, but also the overall meeting. This is, as you said, an unmet need for many reasons. And one of the things that we heard from the patient advocates that were present at the meeting is exactly what you said. That if there's a toxicity that gets graded as one or two, but it really affects the patient's quality of life longterm, that clearly is more important to the patient.
Now, from your perspective, would you, as a medical oncologist and uses a lot of toxic systemic drugs, consider that as something as part of toxicity reporting or PRO reporting? What's your thought there?
Shilpa Gupta: I think it would be both, Ashish and I know we all have patients who get some of the extreme side effects. And I think I was particularly impressed by this patient of mine who was on a clinical trial with immunotherapy and he had some of the worst bladder spasms that none of our urologists had experienced, none of our radiation oncologists had experienced, and this patient's quality of life just became miserable. He could not work anymore, and he had so many cystoscopies, so many drugs that were given to him, and ultimately it became his biggest problem while we tackled the cancer.
And I think from that perspective, when you see the patient as a whole, it certainly should be classified as a toxicity, even if it is rare, and a PRO. Because we have all these other therapies we can use to treat patients and immunotherapy is a big advancement in this, but when it leads to such rare toxicities, it certainly can be debilitating. So I think the PRO work that Dr. Psutka is leading, I'm sure that will address some of these nuances.
Ashish Kamat: Yeah, no, there's obviously still a lot of work for us to do from the retreat, but it's great to have so many people that came together, a common mission, common goal, and work on this. From your perspective, Dr. Gupta, what would it take to get broad buy-in from the community to utilize something like this? Because obviously we want to propose something that'll help the community. Everybody at the retreat was interested, folks that we've talked to, patients, everybody wants to see this happen, but there's an inertia when development of these things in clinical trial adaptation. So just share with us what you think it would take to get this more broadly adapted.
Shilpa Gupta: Yeah, I think that's a great point. We could come up with a grading scale, but if people are still using the historical scales like the CTCAE, which by the way is getting updated soon to version six, it won't really reach the masses and the community. So I think it would be a great idea to talk to the NCI about using this as a complement. Not to replace CTC, but to add as a complement for the bladder-related toxicities. I think that would give people more of an idea and to use this as a guide. And I would love to hear how you think we could do that. I mean, you have been instrumental in involving the FDA with the work led by IBCG, and I'm sure NCI would be interested at the CTEP, right?
Ashish Kamat: Yeah, no, absolutely. And obviously my interactions when I was leading SITC's SIG program and of course interactions with the FDA, EMA, and folks at the NCI, as you said, it's not our goal to replace anything, it's to complement what's already being done and actually make it easier for investigators and pharmaceutical companies and everybody really that's doing this work to be able to quantify things better. Because clearly the better we quantify it, the better we can report it. And then of course, you can compare even though they're not supposed to, across trials, but you clearly can then advise the patients better.
So I think what's nice is that all the stakeholders have the patient interest at heart. And because we are all doing this with the ultimate goal of improving outcomes for patients, everybody at CTEP, NCI, FDA, EMA, SITC, everybody that I've at least had the fortune of talking to is very supportive of similar or this and similar efforts. So I think that would be one way to get it out there.
Shilpa Gupta: And I think another idea would be to, I know we were on the SITC Immunotherapy Guidelines committee to vet it to the SITC, because that's a widely used tool also, and they have an app for it. And I think that would be really good to come up with a companion toxicity grading for SITC, specifically for immunotherapy.
Ashish Kamat: Absolutely. Shilpa, thank you always for taking the time. This is a great report and looking forward to seeing what the group comes together with. In our publication I'm sure we'll feature that again on UroToday and have you back.
Shilpa Gupta: Thank you, Ashish. See you soon. Bye-bye.