Charles Ryan: Hello from SOGUG 2022. I'm speaking with Dr. Ignacio Pelaez from Estudias, Spain, where he specializes in genitourinary oncology and has a particular interest in kidney cancer. Today, we're going to talk about second line kidney cancer in Spain and Europe in general, and how to make a choice amongst all of the therapies that are available. Thank you for joining us.

Ignacio Pelaez: Thank you. Really, the landscape of the treatment of the second line is really difficult because we depend on going with what we use in the first line. In Spain, until a year ago, we used the TKI in monotherapy, and the more robust data in second line is another TKI or monotherapy with immunotherapy. We're talking about the cabozantinib with the METEOR study or the CheckMate-025 with nivolumab. Both of them improve overall survival.

We also have data on combinations after TKI monotherapy. We are talking about lenva/everolimus with a phase II randomized trial, where we can see improving PFS and also in overall survival for the combination against everolimus. We also have data for a phase II trial with lenvatinib and pembrolizumab. This is a phase II with different first line. In the group with first line with TKI, we have really an interesting overall response rate with 58%, and PFS about 10, 11 months.

If we are talking about first line with the combination, we have to separate or choose between an IO, we're talking about ipilimumab and nivolumab, and EOBF with different combination in immunotherapy and TKIs. This is really challenging because we don't know what to do, really, with these patients. We can think that the most robust data is with TKI monotherapy with a different TKI used in the first line. If we are talking about EOBF or we are talking about immuno immuno, TKI monotherapy is probably the best option.

We have also data with combination after combinations, but this is data less solid and we're talking about phase II trials with no more patients. Well, I think to make resume with that. After combination, I think TKI has the robust data.

Charles Ryan: So, the most important choice in second line would be to treat somebody with a class of drug they have not yet received.

Ignacio Pelaez: Sure.

Charles Ryan: Second consideration might be if they've had a combination with a TKI and immuno, axi/pembro, et cetera, that you switch them, you switch the agents. You could still switch to a TKI immuno, but there would be different agents. Or go with another TKI as monotherapy.

Ignacio Pelaez: Sure. I think there are many options, conceptual options, but we have to check clinical trials.

Charles Ryan: Yes.

Ignacio Pelaez: I think it's quite difficult to make a clinical trial in second line because the first line is changing so quickly. So, we don't have time really to make a phase III with standard options.

Charles Ryan: In trials in the second line setting, is PFS and adequate outcome measure for clinical benefit in those patients?

Ignacio Pelaez: Yes.

Charles Ryan: Or do we need overall survival data?

Ignacio Pelaez: That's a good issue because we used to check only PFS when we are talking in first line with TKIs. After that, the combinations in first line choose all that data to overall survival. I think really in the second line, we will try to check overall survival. Because what we want, we want that our patients live more time. We are getting that in first line. Try to get this in second line.

Charles Ryan: Very good. Well, thank you very much for your thoughts. Always interesting to hear what's going on in different countries as they approach the same problems that we all face but with different regulatory constraints all looking at the same data from all of the clinical trials. So, thank you so much and thank you for welcoming us to SOGUG.

Ignacio Pelaez: Okay, thank you for you. It's an honor for me.