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Practical Considerations for Treating With Sorafenib

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:
The optimal patient for sorafenib would be somebody who I don’t feel is in danger of progressing rapidly. Sorafenib causes some shrinkage, although it may not cause a lot of shrinkage. So I’d like to see somebody who is not rapidly progressing but is definitely progressing—and is at risk for developing symptoms from their disease—use sorafenib.

I prefer to use sorafenib in a patient who I don’t want to respond too rapidly. There are sometimes areas that are critical. If they respond too fast, they could have problems. An example of this is somebody who has possible tracheal invasion or an esophageal invasion, or very invasive disease in the neck. I’m afraid that I could shrink it too quickly, causing fistulas or other catastrophic complications. So I want to use this in somebody who I want to get a slow and steady response.

Occasionally there are patients who, for various reasons, are not good candidates for the other kinase inhibitors—mostly lenvatinib, which is the other one that’s out there. If there are comorbidities that they’re particularly at risk for, they might be put on sorafenib first because they may manage it a bit better. The side effect profiles of the different drugs are different. For that reason, I will often use sorafenib first in somebody if I’m worried about comorbidities. Because of adverse effects, and because of invasive disease in somebody who is progressing on a more even keel or at a slower pace—those are people who would probably be ideal for getting treated with sorafenib.

Eric J. Sherman, MD: In deciding who is appropriate for treatment with sorafenib, we recommend for patients who need to start systemic therapy, are having a doubling time of their tumor within 6 months, and are starting to become symptomatic or have disease growing in an area that’s going to cause severe symptoms in the near future. These are the patients we often want to put on sorafenib. The thing you always have to consider is, are you going to choose sorafenib or another drug? Sorafenib has shown to be effective in the first-line setting based on the DECISION study. However, it’s hard to say that sorafenib works that well in a second- or third-line setting.

Other drugs, like lenvatinib and cabozantinib, have been shown to work very well in the second-line setting. For that reason alone, sorafenib in the first-line setting makes a lot of sense. The trade-off is that the response rate and the progression-free survival that we see with sorafenib is actually much less than you see with lenvatinib, cabozantinib, or pazopanib. They have not been compared head-to-head, so we are looking at individual, different studies. It’s not the right way of doing things, but there seems to be a big enough difference. Most people seem to agree that that response rate and progression-free survival from sorafenib is shorter.

So if you have a person with more aggressive disease, or someone for whom you really need to increase the chance of getting a response, using one of these other drugs might be a better option. However, for a lot of patients, if you are starting them on treatment with enough time, starting them on sorafenib can really work. The other drugs can be almost as effective in the second-line setting. You can really give your patient a nice extra benefit. You can go from one drug to another.

For most of my patients with thyroid cancer, this is like running a marathon, not a sprint. If you run a sprint, you go to your best drug and use it right away. If you’re running a marathon, you are going to be going from one drug to another, to another. You don’t need to use the best drug. You need to figure out what is going to be the best sequence of drugs to give the longest period of disease control.

Johannes (Jan) Smit, MD, PhD: My personal experience with sorafenib is that we treat many patients with sorafenib on our team. It’s a drug that really can make a difference in patients with progression of thyroid cancer who are resistant to radioactive iodine. It can give tumor regression in quite a number of patients and can also resolve symptoms. On the other hand, we know that we cannot cure patients. In the end, many patients will have progression. Management of side effects is a very important issue.

The treatment and management of side effects should also be done in a setting where there is much experience in managing side effects. Side effects can be prevented, at least hand-foot syndrome, or can be managed in such a fashion that a patient’s quality of life can be preserved as much as possible. So the experience with sorafenib on our team is extensive, and we are convinced that our setting is necessary when providing optimal treatment to our patients.


Transcript Edited for Clarity
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Transcript: 

Marcia S. Brose, MD, PhD:
The optimal patient for sorafenib would be somebody who I don’t feel is in danger of progressing rapidly. Sorafenib causes some shrinkage, although it may not cause a lot of shrinkage. So I’d like to see somebody who is not rapidly progressing but is definitely progressing—and is at risk for developing symptoms from their disease—use sorafenib.

I prefer to use sorafenib in a patient who I don’t want to respond too rapidly. There are sometimes areas that are critical. If they respond too fast, they could have problems. An example of this is somebody who has possible tracheal invasion or an esophageal invasion, or very invasive disease in the neck. I’m afraid that I could shrink it too quickly, causing fistulas or other catastrophic complications. So I want to use this in somebody who I want to get a slow and steady response.

Occasionally there are patients who, for various reasons, are not good candidates for the other kinase inhibitors—mostly lenvatinib, which is the other one that’s out there. If there are comorbidities that they’re particularly at risk for, they might be put on sorafenib first because they may manage it a bit better. The side effect profiles of the different drugs are different. For that reason, I will often use sorafenib first in somebody if I’m worried about comorbidities. Because of adverse effects, and because of invasive disease in somebody who is progressing on a more even keel or at a slower pace—those are people who would probably be ideal for getting treated with sorafenib.

Eric J. Sherman, MD: In deciding who is appropriate for treatment with sorafenib, we recommend for patients who need to start systemic therapy, are having a doubling time of their tumor within 6 months, and are starting to become symptomatic or have disease growing in an area that’s going to cause severe symptoms in the near future. These are the patients we often want to put on sorafenib. The thing you always have to consider is, are you going to choose sorafenib or another drug? Sorafenib has shown to be effective in the first-line setting based on the DECISION study. However, it’s hard to say that sorafenib works that well in a second- or third-line setting.

Other drugs, like lenvatinib and cabozantinib, have been shown to work very well in the second-line setting. For that reason alone, sorafenib in the first-line setting makes a lot of sense. The trade-off is that the response rate and the progression-free survival that we see with sorafenib is actually much less than you see with lenvatinib, cabozantinib, or pazopanib. They have not been compared head-to-head, so we are looking at individual, different studies. It’s not the right way of doing things, but there seems to be a big enough difference. Most people seem to agree that that response rate and progression-free survival from sorafenib is shorter.

So if you have a person with more aggressive disease, or someone for whom you really need to increase the chance of getting a response, using one of these other drugs might be a better option. However, for a lot of patients, if you are starting them on treatment with enough time, starting them on sorafenib can really work. The other drugs can be almost as effective in the second-line setting. You can really give your patient a nice extra benefit. You can go from one drug to another.

For most of my patients with thyroid cancer, this is like running a marathon, not a sprint. If you run a sprint, you go to your best drug and use it right away. If you’re running a marathon, you are going to be going from one drug to another, to another. You don’t need to use the best drug. You need to figure out what is going to be the best sequence of drugs to give the longest period of disease control.

Johannes (Jan) Smit, MD, PhD: My personal experience with sorafenib is that we treat many patients with sorafenib on our team. It’s a drug that really can make a difference in patients with progression of thyroid cancer who are resistant to radioactive iodine. It can give tumor regression in quite a number of patients and can also resolve symptoms. On the other hand, we know that we cannot cure patients. In the end, many patients will have progression. Management of side effects is a very important issue.

The treatment and management of side effects should also be done in a setting where there is much experience in managing side effects. Side effects can be prevented, at least hand-foot syndrome, or can be managed in such a fashion that a patient’s quality of life can be preserved as much as possible. So the experience with sorafenib on our team is extensive, and we are convinced that our setting is necessary when providing optimal treatment to our patients.


Transcript Edited for Clarity
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