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Differentiated Thyroid Cancer: Sequencing of MTK Inhibitors

Insights From: Marcia S. Brose, MD, PhD Abramson Cancer Center; Johannes Smit, MD, PhD Radboud University Nijmegen Medical Center
Published: Friday, Dec 14, 2018



Transcript: 

Marcia S. Brose, MD, PhD:
So the issue that faces us now, when we’re using both lenvatinib and sorafenib together, is what order do we give them in? This is a question that I’m asked all the time. Unfortunately, we’ll never have the exact answer because we don’t have a study to help determine this. A study like this, unfortunately, would require so many patients that it would never be done. So we’re never going to actually have that answer.

We do know from the SELECT study that patients who get sorafenib first still respond quite well to lenvatinib in the second-line setting. Unfortunately, we don’t have that data in the other order yet. So that’s one thing that makes people sometimes choose to give sorafenib first. However, due to the fact that lenvatinib has these rapid responses, it really becomes a patient-selection issue. There will be patients we will select one or the other based on comorbidities, how well they’ll tolerate hand-foot skin reaction, and how well they will tolerate the hypertensive issue that happens with lenvatinib. How much do they need a rapid response? How much at risk are they because of that rapid response? If they get that rapid response, are they going to end up with fistulas?

As you can see, there are almost as many factors for one drug as there are for the other. What you really need to do is become experienced with both drugs. I don’t tell the patient that one is better than the other. All my patients will get both. At the end of the day, it’s sort of a moot point to say which option is appropriate to use first. I choose the drug that I think will be better tolerated and give me the response that I need in a safe way. If they progress or don’t tolerate the first drug, they will get the second one. So I don’t want to say to them, “Oh, take this one first. It was better than the other one.” At the end of the day, both of these will play a role in every patient’s life, especially in places where both drugs are available. In some countries, that decision is made for you because only one option is available.

In both cases, when a patient progresses on one, I am still going to try to expand the duration and will try to maintain as good and as long of a clinical benefit with each drug. Just because they have 1 progression site, I won’t necessarily switch immediately. At that point, I’ll try to treat it locally, maintain that first drug for as long as it’s clinically beneficial, and then, when it looks as if it’s really not working as well, I will switch to the other agent.

Eric J. Sherman, MD: The big thing I have to mention with lenvatinib is to go down in dosage if the person is not tolerating it. Part of this is about quality of life. This is a different cancer than pancreatic cancer or metastatic lung cancer. You don’t need to be pushing the highest dosage possible to get benefit. One of the important things is really trying to help patients with their quality of life. There’s no point in making them miserable. I tell all my patients that with whatever drug we’re putting you on, if I’m not getting you out of bed, and you aren’t doing your normal activities, we’re failing at what we’re doing and need to make adjustments.

I do let them know that they’re going to have side effects in the beginning and that it’s going to take a little while to make those adjustments. We will have to make those adjustments because people should be fully functional on whichever medication that we put them on. We need to get them on the right [dosage] of therapy and provide them with supportive care so that they are able to function.


Transcript Edited for Clarity
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Transcript: 

Marcia S. Brose, MD, PhD:
So the issue that faces us now, when we’re using both lenvatinib and sorafenib together, is what order do we give them in? This is a question that I’m asked all the time. Unfortunately, we’ll never have the exact answer because we don’t have a study to help determine this. A study like this, unfortunately, would require so many patients that it would never be done. So we’re never going to actually have that answer.

We do know from the SELECT study that patients who get sorafenib first still respond quite well to lenvatinib in the second-line setting. Unfortunately, we don’t have that data in the other order yet. So that’s one thing that makes people sometimes choose to give sorafenib first. However, due to the fact that lenvatinib has these rapid responses, it really becomes a patient-selection issue. There will be patients we will select one or the other based on comorbidities, how well they’ll tolerate hand-foot skin reaction, and how well they will tolerate the hypertensive issue that happens with lenvatinib. How much do they need a rapid response? How much at risk are they because of that rapid response? If they get that rapid response, are they going to end up with fistulas?

As you can see, there are almost as many factors for one drug as there are for the other. What you really need to do is become experienced with both drugs. I don’t tell the patient that one is better than the other. All my patients will get both. At the end of the day, it’s sort of a moot point to say which option is appropriate to use first. I choose the drug that I think will be better tolerated and give me the response that I need in a safe way. If they progress or don’t tolerate the first drug, they will get the second one. So I don’t want to say to them, “Oh, take this one first. It was better than the other one.” At the end of the day, both of these will play a role in every patient’s life, especially in places where both drugs are available. In some countries, that decision is made for you because only one option is available.

In both cases, when a patient progresses on one, I am still going to try to expand the duration and will try to maintain as good and as long of a clinical benefit with each drug. Just because they have 1 progression site, I won’t necessarily switch immediately. At that point, I’ll try to treat it locally, maintain that first drug for as long as it’s clinically beneficial, and then, when it looks as if it’s really not working as well, I will switch to the other agent.

Eric J. Sherman, MD: The big thing I have to mention with lenvatinib is to go down in dosage if the person is not tolerating it. Part of this is about quality of life. This is a different cancer than pancreatic cancer or metastatic lung cancer. You don’t need to be pushing the highest dosage possible to get benefit. One of the important things is really trying to help patients with their quality of life. There’s no point in making them miserable. I tell all my patients that with whatever drug we’re putting you on, if I’m not getting you out of bed, and you aren’t doing your normal activities, we’re failing at what we’re doing and need to make adjustments.

I do let them know that they’re going to have side effects in the beginning and that it’s going to take a little while to make those adjustments. We will have to make those adjustments because people should be fully functional on whichever medication that we put them on. We need to get them on the right [dosage] of therapy and provide them with supportive care so that they are able to function.


Transcript Edited for Clarity
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