Sequencing Treatments for NTRK-Positive Thyroid Cancer

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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 NTRK-positive thyroid cancer.

Cancers associated with the NTRK 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 NTRK 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 NTRK 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.

TRANSCRIPTION:

0:08 | Whenever I would imagine having a patient with the NTRK-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.