Pedro Barata: I'm very happy to be joined today by Dr. Takemura. Dr. Takemura is a urologist and doing a medical oncology fellowship with Dr. Daniel Heng in Calgary, Canada. And so welcome Dr. Takemura.

Kosuke Takemura: Thank you very much.

Pedro Barata: Thank you for taking the time to be with us today.

Kosuke Takemura: My pleasure.

Pedro Barata: Congratulations on your work. Great presentation at ASCO GU, important project. It comes out of the IMDC database, right? Specifically looking at patients with brain metastasis. So I guess first things first, I know a lot of us are familiar with IMDC, but perhaps here's for those who might be less familiar with it, can you just review the structure of this international big database of patients around the world with kidney cancer?

Kosuke Takemura: So IMDC stands for International Metastatic RCC Database Consortium and we are currently collecting the data from over 40 institutions around the world. Yeah, IMDC was initially created by Dr. Daniel Heng, who's my mentor in Calgary and also by Dr. Tony Choueiri at Dana Farber Cancer Institute. And we are trying to assess the patients' demographics and the outcomes based on the database. And one of our previous important findings is that IMDC criteria, which consists of the six risk factors, can classify the patient's prognosis very well. And the IMDC criteria is currently used for many clinical trial design and also risk stratifications for patients with metastatic RCC.

Pedro Barata: Got it. Great. Now that's great job. So let's talk specifically about the work that you presented at ASCO GU, right? So large database and you look specifically at patients with brain metastasis and actually you compare outcomes and you compare those group of patients against those without brain metastasis, right? So I guess can you highlight what was the take home points about maybe the patient, the disease characteristics, right? Of that group of patients, if you will? What came out that would be relevant for the treating physician out there?

Kosuke Takemura: All right, yeah. So in this study we qualified three points. So the question one was how high is the instance of the RCC brain metastasis at start of systemic therapy? And the answer was 7.9% amongst the whole patients with metastatic RCC who started first line therapy. So this is not a negligible number and we have to think about brain screening before starting systemic therapy, that is one point. And second question was what are the outcomes and the prognostic factors for patients with brain metastasis? And the answer was that there were four significant prognostic factors. First of all, immuno-oncology combination therapy was associated with longer OS compared with the traditional TKI therapy. And also intermittent risk or favor or intermediate, sorry, intermediate or favorable IMDC risk was associated with longer OS. And also brain-directed therapies such as stereotactic drug surgery or neurosurgery were also associated with long overall survival. So there is question two. And also there was question number three, is there any temporal trends in brain directed therapies? And we found that whole-brain radiotherapy has been declining significantly these days, and instead stereotactic radiosurgery is increasing significantly. So those are three important points we found in the study.

Pedro Barata: No, that's great, very important. And I'm thinking as we're talking, right, as a treating physician, can you kind of tell us from your analysis, if you will, were there any patterns as far as managing these patients, right? You told us about the patient characteristics and also the disease characteristics. Did you identify any patterns about a tendency, what doctors tend to do when they encounter patients with brain metastasis, and whether or not that actually changes for patients that present with de novo brain metastasis versus those who actually progress on systemic therapy with newly diagnosed brain metastasis? Right.

Kosuke Takemura: Yeah.

Pedro Barata: Can you tell us a little bit of what it has been, the practice in your study?

Kosuke Takemura: Okay. So in terms of the systemic therapy, we found that IO-based therapy was mainly nivolumab-ipilimumab therapy. And we found that there was also some trends in brain-directed therapies as I explained. So there was an increased number of the stereotactic radiosurgery given to the patient, and as a result, the patients are probably benefiting from the more combination therapy, so the systemic therapy and brain-directed therapies altogether. So overall, we would suggest that we have to think about a multidisciplinary approach for patients with brain metastasis, including more effective systemic therapies such as immuno-oncology therapy and also the brain-directed therapies such as stereotactic radiosurgery or neurosurgery for applicable.

Pedro Barata: Got it. No, that's very helpful and I really think it's important to have real-world data for this particular group of patients. We were chatting earlier today about a lot of these patients unfortunately get to be excluded from clinical trials.

Kosuke Takemura: That's true.

Pedro Barata: Right? And so having that data out there helps the treating physician how to manage, best manage, these patients. Perhaps let me ask you, is there anything else from your project with Dr. Heng that you'd like to highlight for our audience?

Kosuke Takemura: We suggest that brain metastasis at the start of systemic therapy is relatively high proportion. So it's just slightly less than 10%. So we have to think about brain screening before starting systemic therapy because this might potentially change the treatment strategies. So even for patients with asymptomatic brain metastasis, we might have to think about brain-directed therapies. And also another question we encountered through this study is that when we think about total treatment strategies, we have to think about the sequence of the appropriate treatment for patients with brain metastasis, namely patients might benefit from starting the brain-directed therapies first. And then we can try to think about more intensive systemic therapies such as immuno-oncology based combination therapies. Because in general, patients with brain metastasis have a poor performance data or brain metastasis related symptoms such as severe headaches or seizures. So we might probably have to control those symptoms related to the brain, direct brain metastasis. Then after that we can think about more intensive treatment.

Pedro Barata: Got it.

Kosuke Takemura: And also, while patients are receiving brain-directed therapies, patients are usually given some sort of steroid. And steroid is known to reduce the efficacy of the immuno-oncology therapy. So it is reasonable to wait for the steroid tapering after completion of brain-directed therapies, then we can think about immuno-oncology combination therapy.

Pedro Barata: Those are very important points out there. We don't necessarily screen everybody, and so that's definitely a powerful message. Not that different, not that far from 10%, it'll be shy from the 10% prevalence of brain metastasis. So important, complete staging is a very important message. And then prioritizing local therapy seems to be really relevant. And we have a couple of data actually showing that the efficacy of systemic therapies, or untreated brain mets is not actually optimal. So very, very important points to the treating physicians out there. Thank you so much for coming today, being generous with us and having a wonderful discussion. I know, I'm just looking forward to read the paper and get the access to the full data.

Kosuke Takemura: Oh yeah.

Pedro Barata: We all want that. It's very important. So congratulations again. Great job.

Kosuke Takemura: Yeah.

Pedro Barata: And hope to see you soon. Thank you.

Kosuke Takemura: My pleasure, thank you for your time.