TRK Inhibitors for Advanced Thyroid Cancers


Important takeaways from recent safety and efficacy data presented on the use of larotrectinib as treatment for advanced differentiated and anaplastic thyroid cancers with NTRK gene fusions.

David S. Hong, MD: Let me comment on the presentation of our most recent data set that we presented, concerning larotrectinib in the treatment of advanced-NTRK fusion thyroid cancer, presented by my colleague at [The University of Texas] MD Anderson [Cancer Center], Dr Kevin Nead. Stepping back, 1 of the most common tumor types actually is thyroid cancer. We’ve identified NTRK fusion in not only the more common papillary phenotype but also in follicular. Close to 25% of these patients with NTRK-fusion thyroid cancers are very aggressive anaplastic phenotypes. In this data set that Dr Nead has presented, there were close to 28 patients who were analyzed from our data set, 68% being papillary, a small percentage of 7% being follicular, and close to 25% being anaplastic. The majority of these patients interestingly, will either harbor NTRK1 or NTRK3. NTRK3 fusions can often be missed unless you have an RNA-based NGS [next-generation sequencing]. The majority of these patients were iodine refractory or systemic therapy refractory and had greater than 2 to 3 lines of therapy.

The overall response rate was close to 90%. In the anaplastic, the response rate was close to 30% or 29%. One could argue that that tells you the different histologies and the different biology of the tumors. Similar to the primary CNS cohort, these patients with anaplastic are very aggressive, and a response rate of 30% is fairly remarkable because they oftentimes do not respond to standard chemotherapy or other therapies. The duration of response in this cohort was again not reached. With a median follow-up of 10.2 months, the median progression-free survival again was not reached, the median follow-up of 12.8 months, and the overall median survival was 27.8 months in this subset.

Similar to the other patients in the larotrectinib safety profile, the vast majority of the patients who had received the drug experienced grade 1 or 2 toxicities, the most common being fatigue, constipation, and some dizziness. The vast majority of these patients tolerated therapy very well. These patients with NTRK fusion and thyroid tend to be, in this context, younger patients who do not have other alterations, such as BRAF or RET alterations. If you find a patient who is younger, who does not have all other alterations, in particular in the context of anaplastic, it is worth exploring and seeing if we can identify NTRK-fusion patients. Overall, these patients—and I’ve treated a majority of these patients in this data set with larotrectinib—have remarkable responses and will stay on study for years. Several of my patients have remained on study for 5, 6 years. On this trial, 1 of my anaplastic patients, which is an aggressive tumor, was able to stay on the study for close to a year with good quality of life. If these patients with ETV6, NTRK3, or any other NTRK alteration is identified, the benefit from this therapy can be life-changing for them.

Transcript edited for clarity.

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