Sequencing Therapies in the Second Line and Beyond in Advanced RCC


Dr Barata comments on sequencing therapies in the second line and beyond in patients with advanced RCC.

Tian Zhang, MD: In thinking about all these treatments and strategies, how are you all sequencing these agents in the second line and higher? Dr Barata, perhaps you can give us your insights on this?

Pedro C. Barata, MD, MSc: That’s a great question, Tian. We can spend a good deal of time going over that. I’ll try to summarize it shortly. When I think of the options available, my colleagues highlighted important studies that leverage those therapies. Cabozantinib is a very solid option. Axitinib is another option. Tivozanib a new 1 but is definitely part of this group. And the combination of lenvatinib and everolimus. A lot of us think of those 4 as ready to use. That’s true because we have access to these therapies in the United States, but in other places in the world, after first-line I/O [immuno-oncology]–based combo therapy, folks are still using pazopanib-sunitinib in the refractory space. But those 2 agents have less prospective data available to be used in the refractory space.

When we think of what data are out there to support the use of therapies, I have to highlight the data with cabozantinib and with axitinib in the post-immunotherapy setting. I can think of studies supporting either agent in that scenario. Other factors, like quality of life, are important to Moshe’s point. I see tivozanib as a very clean agent. We think of high blood pressure, but that’s relatively easy to manage, so it’s a really clean agent. That’s a factor that’s sometimes important when I’m thinking quality of life.

It does matter what patients received previously. If they received ipilimumab-nivolumab up front, what are we going to do afterward? It’s very different for patients treated with up front cabozantinib-nivolumab or axitinib-pembrolizumab or lenvatinib-pembrolizumab, because we tend not to repeat that agent in the second line. The other thought process out there is that some folks try to stay away from immunosuppressive agents; mTOR has those properties, like everolimus. Thus, we try not to use lenvatinib-everolimus after an I/O–based combo in the front line, although we lack prospective data showing the impact of using immunosuppressives to know whether it’s detrimental in patients with refractory RCC.

We also consider other factors, like location, for metastatic disease. I believe 1 of us mentioned that for patients with bone metastasis, for example, perhaps cabozantinib has done a good job. Even concerning genomics, we know that, unfortunately, we don’t have high rates of targetable alterations in RCC [renal cell carcinoma]. But we still do it. All patients step into clinic, and most clinics get somatic testing done. If I have a patient where TSC1, tuberous sclerosis gene, mutated, I’m thinking of mTOR, right?

I have to highlight that there are ongoing trials in the refractory space exploring the role of a checkpoint inhibition combo at postprogression on the prior I/O therapy. We have some data from Memorial [Sloan Kettering Cancer Center]. Although we have less time, we have more data coming up. I guess this is a least a big list of factors. We have the patient in front of us, so I guess we have to make sense of it all it and come up with what we think is the best strategy for our patient. But if I were to summarize, I’ll say 1 size does not fit all. We’re try to make sense of all this.

Tian Zhang, MD: That’s a wonderful summary in helping us decide.

This transcript has been edited for clarity.

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