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The RIFTOS MKI Study in Differentiated Thyroid Cancer

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: 

Johannes (Jan) Smit, MD, PhD: At this point, we really do not know exactly when treatment with multikinase inhibitors should start. We have very rough guidelines that tell you that the patient should be progressive, that tumor volume should be considerable, and that the patient should be radioactive iodine resistant. We do not know what rate of progression is required for optimal treatment. We do not know an exact cutoff for tumor volume. So there is a lot that we do not know at this moment.

Marcia S. Brose, MD, PhD: When people ask me when we should start with multikinase inhibitor therapy, as a purist I say that we have the data from the DECISION study or from the SELECT study that says that you should start it when patients no longer benefit from radioactive iodine because it’s no longer avid or is growing in spite of iodine. They have progression of their disease and have detectable disease based on RECIST [response evaluation criteria in solid tumors] criteria, which means that they have at least 1 nodule that’s 1 centimeter. So that was the eligibility criteria for the trials, and I’d say that’s the bare minimum for what we would require for starting with kinase inhibitors.

How people will then use that information is very broad. Will they start immediately, at that point? Will they think that it’s better to hold off for a while and then start later? We really didn’t have the answer to that question and there was concern that we didn’t want to give people toxicity when they had a very low burden of disease. The growth rate was very slow, and we knew they were going to be asymptomatic for quite a while. Why give them the adverse effects of the treatment if they weren’t going to even have side effects from the disease, so to speak?

Because of that, we wanted to answer that question. The design of the RIFTOS MKI study asked that question. If we have people who meet that criteria, we’re now going to look at the difference between the people who are started on therapy right away versus people who are held off for a while. We can see if there’s any difference in the outcome. Do they do better or worse? Do they live longer or not? What are the differences between those 2 groups? We truly want to answer the question: Should we be treating people right away, or should we wait a little longer?

Johannes (Jan) Smit, MD, PhD: The RIFTOS MKI trial has been designed to address when the optimal time to initiate tyrosine kinase inhibitor treatment is. The trial is a noninterventional international trial, and the most important endpoint is time to symptomatic progression. Two groups of patients are being compared. Both groups contain asymptomatic patients. One group contains patients who already have been treated with tyrosine kinase inhibitors at baseline. The other group contains patients who have not received a tyrosine kinase inhibitor.
The trial is very important because, at this moment, there is not a clear guideline that tells you when to start systemic therapy. Of course, in the indications, it’s set out that patients should be progressive and that there should be radioactive iodine resistance. But this includes a whole spectrum of conditions. Many colleagues tend to interpret those frames differently. From this trial, we hope to learn when the optimal time to start therapy is. In this respect, the trial will be practice changing. At this moment, we do not have a clear guidance on how to deal with this question.

Marcia S. Brose, MD, PhD: The results of the RIFTOS MKI trial, which are aimed to determine whether starting early or starting late is optimal for the patient, could be practice changing, depending on what the results of the trial are and what you already do. It may turn out that you should really start treating earlier rather than later. If that is determined, then people who have been holding off until symptoms develop or for longer periods of time will probably change their practice. The interesting thing is, it will be practice changing because there’s such a large variety right now in what people do. I think it will probably help guide people into more of a consistent approach to when therapy should be started with the kinase inhibitors.

Johannes (Jan) Smit, MD, PhD: The importance of the RIFTOS MKI trial for community oncologists is that it will help them determine the optimal time point for initiating systemic therapy in thyroid cancer patients. But having said that, I really believe that the treatment of thyroid cancer should take place in centers that are specialized in this treatment. This is a disease that is of low prevalence. We really need to manage these patients in a multidisciplinary fashion. All treatment decisions in our institute are being made by a multidisciplinary team. So I think it’s very important for community oncologists to be a part of a multidisciplinary structure. In that setting, the RIFTOS MKI trial will help them make decisions on the initiation of kinase inhibitor treatment.


Transcript Edited for Clarity
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Transcript: 

Johannes (Jan) Smit, MD, PhD: At this point, we really do not know exactly when treatment with multikinase inhibitors should start. We have very rough guidelines that tell you that the patient should be progressive, that tumor volume should be considerable, and that the patient should be radioactive iodine resistant. We do not know what rate of progression is required for optimal treatment. We do not know an exact cutoff for tumor volume. So there is a lot that we do not know at this moment.

Marcia S. Brose, MD, PhD: When people ask me when we should start with multikinase inhibitor therapy, as a purist I say that we have the data from the DECISION study or from the SELECT study that says that you should start it when patients no longer benefit from radioactive iodine because it’s no longer avid or is growing in spite of iodine. They have progression of their disease and have detectable disease based on RECIST [response evaluation criteria in solid tumors] criteria, which means that they have at least 1 nodule that’s 1 centimeter. So that was the eligibility criteria for the trials, and I’d say that’s the bare minimum for what we would require for starting with kinase inhibitors.

How people will then use that information is very broad. Will they start immediately, at that point? Will they think that it’s better to hold off for a while and then start later? We really didn’t have the answer to that question and there was concern that we didn’t want to give people toxicity when they had a very low burden of disease. The growth rate was very slow, and we knew they were going to be asymptomatic for quite a while. Why give them the adverse effects of the treatment if they weren’t going to even have side effects from the disease, so to speak?

Because of that, we wanted to answer that question. The design of the RIFTOS MKI study asked that question. If we have people who meet that criteria, we’re now going to look at the difference between the people who are started on therapy right away versus people who are held off for a while. We can see if there’s any difference in the outcome. Do they do better or worse? Do they live longer or not? What are the differences between those 2 groups? We truly want to answer the question: Should we be treating people right away, or should we wait a little longer?

Johannes (Jan) Smit, MD, PhD: The RIFTOS MKI trial has been designed to address when the optimal time to initiate tyrosine kinase inhibitor treatment is. The trial is a noninterventional international trial, and the most important endpoint is time to symptomatic progression. Two groups of patients are being compared. Both groups contain asymptomatic patients. One group contains patients who already have been treated with tyrosine kinase inhibitors at baseline. The other group contains patients who have not received a tyrosine kinase inhibitor.
The trial is very important because, at this moment, there is not a clear guideline that tells you when to start systemic therapy. Of course, in the indications, it’s set out that patients should be progressive and that there should be radioactive iodine resistance. But this includes a whole spectrum of conditions. Many colleagues tend to interpret those frames differently. From this trial, we hope to learn when the optimal time to start therapy is. In this respect, the trial will be practice changing. At this moment, we do not have a clear guidance on how to deal with this question.

Marcia S. Brose, MD, PhD: The results of the RIFTOS MKI trial, which are aimed to determine whether starting early or starting late is optimal for the patient, could be practice changing, depending on what the results of the trial are and what you already do. It may turn out that you should really start treating earlier rather than later. If that is determined, then people who have been holding off until symptoms develop or for longer periods of time will probably change their practice. The interesting thing is, it will be practice changing because there’s such a large variety right now in what people do. I think it will probably help guide people into more of a consistent approach to when therapy should be started with the kinase inhibitors.

Johannes (Jan) Smit, MD, PhD: The importance of the RIFTOS MKI trial for community oncologists is that it will help them determine the optimal time point for initiating systemic therapy in thyroid cancer patients. But having said that, I really believe that the treatment of thyroid cancer should take place in centers that are specialized in this treatment. This is a disease that is of low prevalence. We really need to manage these patients in a multidisciplinary fashion. All treatment decisions in our institute are being made by a multidisciplinary team. So I think it’s very important for community oncologists to be a part of a multidisciplinary structure. In that setting, the RIFTOS MKI trial will help them make decisions on the initiation of kinase inhibitor treatment.


Transcript Edited for Clarity
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