Pedro Barata: Hi, I'm happy to be joined today by Dr. Fabien Moinard-Butot from the Medical Oncology Department in the Strasbourg Cancer Institute. Welcome, Fabien. Thank you for joining us today.

Fabien Moinard-Butot: Thank you for this invitation.

Pedro Barata: Absolutely. Congratulations, you have a very interesting and original concept project, I should say, that you presented at ASCO GU, a great meeting and very interesting concept. And you basically presented the results of exploring local therapy for residual disease for patients achieving complete responses and scans in a cohort of patients with advanced renal cell carcinoma. Maybe I should start by asking you, can you summarize, how did you put that concept together and come up with that idea of reviewing the outcomes of that cohort of patients?

Fabien Moinard-Butot: We performed retrospective single center study at the Strasbourg Cancer Institute. We enrolled 80 patients treated with immunotherapy-based combination with metastatic renal cell carcinoma. The primary endpoint was the complete response rate. We have systemic therapy plus treatment of residual disease, nine out of 80 patients had complete response in our study. And by adding treatment of residual disease, we increased the number of complete responders from nine patients to 19 patients. So we increased the complete response rate from 11% to 24%.

Pedro Barata: Got it. So really interesting concept because you are offering an IO-based approach, which, by the way, let me ask you, can you give us the breakdown exactly what their combos were? Was that ipi-nivo mainly, or did you get IO and TKI combinations?

Fabien Moinard-Butot: Most patients received doublet of immunotherapy, and also patients received immunotherapy plus TKI, and also immunotherapy-based treatment included triplets. Two-third of patients received doublet of immunotherapy.

Pedro Barata: Got it. So two-thirds of your cohort got ipi-nivo, and then those achieving a response, you were able to offer local treatment with the endpoint being complete response. And without doing that, it was around 11%, which is actually very concordant with the ipi-nivo data-

Fabien Moinard-Butot: Yeah.

Pedro Barata:... from CheckMate-214. And then those patients were able to actually improve the CR rate from 11% to close to 20%. So the question that I have, which is a very interesting concept really, kudos to you for conducting that study, is what kind of local treatments did you offer to those patients? What kind of treatments did they get? Was everybody got radiosurgery or some people got actual surgery or radioablation was used? Can you tell us a little bit about exactly what local therapies were offered?

Fabien Moinard-Butot: We performed surgery for nine out of 10 patients received local treatment, and one patient had liver radioablation.

Pedro Barata: Gotcha. So most people were treated with surgery?

Fabien Moinard-Butot: Yeah.

Pedro Barata: Gotcha. Okay. So that's actually a real concept, because we do care about response rate and we do care about complete responses, and we have been seeing that complete responses seem to be durable with long-term follow up data, and perhaps the longest we have known so far is from ipi-nivo, but we start having more longer data with over three years follow up with IO-TKIs, and it seems to be persistent. So where you're really trying to take is more PRs becoming CRs by using local approaches, so I really think that's an original concept and I really like that.

So the question that I have for you is, that's a retrospective effort, big cohort, 80 patients. For one institution, that's a sizable number. Can you share with us what next steps might look like? Because to me is, you probably thinking about prospective validation of this effort. Are you talking to sites to do that? Where are we as far as proving the concept that bringing local therapy down the line is a good idea?

Fabien Moinard-Butot: We want to perform retrospective study with complete responder in a national study.

Pedro Barata: Okay.

Fabien Moinard-Butot: ... for describe the complete responder characteristics. And maybe the next future, in the prospective study, with patients responding immunotherapy, maybe two arms, one with surgery and one without surgery.

Pedro Barata: Gotcha. So right now, you're in the process of finding other sites. Are you looking at across different European countries, for instance? You're thinking about having another sites helping you beyond Strasbourg? I'm curious to know, because actually, forums like ASCO GU, if you're thinking about that, I'm sure during ASCO GU you found a lot of investigators interested in helping you with that effort.

And the other question that I might have for you is, some of these patients, or that we see in clinic at least, have a primary tumor in place. They have renal mass in addition to metastatic sites. Were those patients included in your cohort, or your cohort only included patients that had metastatic lesions, but there was no primary mass in place?

Fabien Moinard-Butot: The pre-nephrectomy was performed for only 46% of patients in our study.

Pedro Barata: Okay.

Fabien Moinard-Butot: And so, the treatment of residual disease, four patients had nephrectomy.

Pedro Barata: Okay.

Fabien Moinard-Butot: Two patients had nephrectomy plus lymph node dissection, and all the patients had lung resection, lung resection plus lymph node dissection, and retroperitoneal lymph node dissection.

Pedro Barata: Got it. So interesting concept, and the reason I was asking for that is because, as you know, it's unsettled yet what the role of deferring the nephrectomy is for patients getting IO-based combos. And there's a couple of important efforts right now ongoing trying to answer that question, perhaps I will highlight one of them, it's called, PROBE Trial, it's a phase three trial that is enrolling across sites in the United States. It's a SWOG effort, but cooperative group's effort really, asking the question about the role of the deferred nephrectomy, so that's going on. And so, data like yours actually leverage these kind of approaches where you have achieved a response, and then in some situations, you might benefit patients from addressing the residual disease, which might be in the kidney or outside the kidney. So it's interesting that you actually have a combination of addressing the primary tumor later on with nephrectomy, or addressing metastatic sites, as you said, with lung resections or lung nodule resections.

So Fabien, this has been amazing. A very important topic. As we talk about novel therapies, I think it's also important to see how we can optimize the outcomes of patients who are being treated with IO-based approaches. And so, I really think concepts like yours are helpful because they can actually leverage good concepts that will be studied and validated prospectively. So thank you for taking the time being here with us, and again, congratulations for your great job.

Fabien Moinard-Butot: Thanks a lot.