Krzysztof J. Misiukiewicz, MD

Krzysztof J. Misiukiewicz, MD, associate professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai and clinical director of the Center for Personalized Cancer Therapeutics at the Tisch Cancer Institute, discusses when targeted therapy may be used for patients with 

Misiukiewicz says that patients with thyroid cancer will first receive surgery and/or radioactive iodine therapy. Those who continue to progress following total thyroidectomy and receiving radioactive iodine need further treatment. Genetic testing can reveal potential targets for therapy including 

, which have different recommended regimens.

 fusion, are iodine-refractory, and have no alternative treatment options are eligible for the NTRK inhibitors larotrectinib (Vitrakvi) and entrectinib (Rozlytrek). These therapies are approved for patients with any solid tumor with an 

 fusion, which can also include salivary gland tumors and soft tissue sarcoma.

According to Misiukiewicz, larotrectinib would be his preferred next line of therapy for any patient with iodine-refractory thyroid cancer with an 

 fusion based on the efficacy seen with NTRK inhibition.

 In thyroid cancer, we treat patients [who] are iodine-refractory, meaning that they underwent total thyroidectomy; they underwent treatment with radioactive iodine and for any reason, those treatments were not effective, and the cancer is still progressing, so we label those patients as iodine-refractory patients. In those situations, those patients are being referred to me, where I do first genetic testing. And then I would consider treating those patients with larotrectinib. So they have to have evidence of progressive cancer that hasn't responded to previous treatments such as surgery or radioactive iodine.

-positive disease, I prefer targeted therapy. Currently we have 2 drugs on the market that are approved; my preferred drug is larotrectinib. That is approved for 

-mutated patients. And this is the drug that usually I choose when I have patients with the 

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Krzysztof J. Misiukiewicz, MD, discusses when targeted therapy may be used for patients with NTRK-positive thyroid cancer. 

When to Use Targeted Therapy for Iodine-Refractory Thyroid Cancer

Krzysztof J. Misiukiewicz, MD, associate professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai and clinical director of the Center for Personalized Cancer Therapeutics at the Tisch Cancer Institute, discusses sequencing of treatments in patients with 

 gene fusion mutation can be treated with targeted tyrosine kinase inhibitors. Larotrectinib (Vitrakvi) is a first-generation NTRK inhibitor approved by the FDA for patients with 

 fusion mutations regardless of tumor tissue type when the tumor is metastatic or nonresectable and has either progressed with treatment or has no alternative treatment options available.

According to Misiukiewicz, patients with thyroid cancer who are 

 positive should receive larotrectinib before other non-targeted treatments that are approved for thyroid cancer. For those whose disease progresses after larotrectinib therapy, he recommends clinical trials of second-generation NTRK inhibitors which are still in development. Other approved thyroid cancer drugs should be considered after larotrectinib as well.

If a patient begins treatment on a drug that is not targeted for a mutation, Misiukiewicz suggests switching to larotrectinib once the other treatment is no longer effective or shows high toxicity.

 Whenever I would imagine having a patient with the 

-positive mutation having a thyroid cancer, I would favor an NTRK inhibitor versus some other treatment that we have, obviously, that are FDA approved. So in this case, I would favor, as a first-line treatment, to give larotrectinib. If I’m going to have a patient that progressed—and I haven’t seen such a patient yet, and I’m hoping to never see [a patient progress] with larotrectinib—I would look for a clinical trial.

There are some second-generation NTRK inhibitors. But there are some other medications approved in thyroid cancers…obviously, I would consider using them if I have a patient that progressed on larotrectinib. If I have the other situation, in which I use one of the drugs that we can use that is not based on the mutational status, such as lenvatinib [Lenvima] or sorafenib [Nexavar] that we can give to [patients with] thyroid cancer…If this treatment is too toxic or just not working, I would definitely switch them immediately to larotrectinib as long as they have the mutation.

Krzysztof J. Misiukiewicz, MD, discusses sequencing of treatments in patients with NTRK-positive thyroid cancer. 

Krzysztof J. Misiukiewicz, MD | Authors

Articles

When to Use Targeted Therapy for Iodine-Refractory Thyroid Cancer

Sequencing Treatments for NTRK-Positive Thyroid Cancer