Reviewing Data on Lenvatinib plus Pembrolizumab Combination Treatment for Advanced Renal Cell Carcinoma - Episode 12

Dosing Lenvatinib for First-Line Renal Cell Carcinoma Treatment

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An explanation of dosing strategies when treating patients with renal cell carcinoma in the first-line with lenvatinib.

Rana McKay, MD: We still have so much to learn about dosing, and we’re now 10 years-plus into TKIs [tyrosine kinase inhibitors] in the clinic and RCC [renal cell carcinoma] beyond that, 15 years, I should say. Monotherapy lenvatinib is 24 mg, when you combine it you’re doing 18 mg, when you combine it with pembrolizumab, you’re doing 20 mg. It gets confusing for people. And the dose titration gets confusing, because they come in 10- and 4-mg tablets. Adjusting the dose takes some skill, and there is an art to being able to do that. The lenvatinib plus pembrolizumab dosing, as I stated, was at 20 mg. The strategy here was to start higher, and rapidly dose reduce if patients are running into toxicity, as opposed to starting more middle of the road, and allowing dose escalation, if you will. The strategy has been to start high and rapidly come down on the dose. We saw the data that came out looking at 18 vs 14 mg, and there did seem to be an impact of starting at a higher dose affecting efficacy. If you’re going to use this regimen, I would use it per the label, which is to start at 20 mg, and then of course, provide a lot of education for the patient and modify as you will. What do you think, Tom?

Tom Powles, MBBS, MRCP, MD: I agree with you. Again, the most important thing when we’re choosing the regimen we want to use now is around supporting patient education, and experience of the regimen. It’s not clear to me which regimen is the best. I’m not sure there is one that’s clearly the best. What I am familiar with is the difficulty we’ve had translating clinical trial results into the real world effectively. And we saw in the United Kingdom in sunitinib that the majority of patients were only getting 2 or 3 cycles, despite progression-free survival originally being 11 months. One of the important steps we have now is around trying to focus; giving combination therapy is more difficult than single-agent therapy. And we need to focus on [treating] the patient effectively using the treatment well.

I agree with you completely. Starting at 20 mg is the right dose, but patients should be told the likelihood is you’ll need to dose reduce, and you shouldn’t feel bad about that. Many patients come to me and say, “I don’t want to dose reduce because it’s a cancer drug and my cancer is going to….” And my take on that is most patients dose reduce. I say the first month of therapy is always a bit of an experiment. We don’t know how many days you’re going to have it, it might be you have a week on and a week off. What’s important that we don’t treat through adverse events because patients can have a terrible experience and that’s why they stop a drug early. We know that there are some weird and wonderful adverse effects of a new therapy, and therefore we need to have really well educated teams, both emergency teams as well as cancer teams, because often the patients are pitching up to emergency departments [EDs] with immune-related problems. The education and training around the adverse event profile and the dosing of these drugs is really important.

Rana McKay, MD: That’s a very good point. I love that you highlighted the point about the teams because it’s so important to actually notify the frontline people about the patients, the regimens they’re on, the adverse effects that they may experience. For example, like our triage team that answers the phones, and your nursing staff, the LVN [licensed vocational nurse] staff, the ED team. Those individuals are critically important in optimizing management and appropriate triage and escalation when things are significant vs education to the patient and reinforcement strategies.

It’s interesting, I just thought of this, when we do chemotherapy, a lot of times we just automatically, prophylactically prescribe, “These are your antiemetics, you don’t need to use them, but you’ve got them.” But they’re embedded into our treatment plans when we do chemotherapy, these medications automatically get sent to the patient’s pharmacy, and they know that they have those medications on deck to use. Adopting that same sort of model of, “This is your Imodium, you don’t need to use it. If you run into issues, you’ve got it. I know there’s a high risk you’re going to get diarrhea, so this is what to do for it. Here’s your udder cream or whatever it is for your rash.” Being prophylactic, “Get your cuff, make sure you have it when you’re gearing up to start the medication.” A lot of times having pharmacists who are able to teach when patients pick up their medications from the pharmacy, “You’ve got everything that you need, you’ve got your cuff, you know what you need to do,” and doing an early check in, is important. Because I think you’re right, the first month, we don’t know what to expect. And it’s different for every single patient, but having expectations be set for everybody is key.

Transcript edited for clarity.