Response to Larotrectinib in NTRK+ Thyroid Cancer Differs By Subtype


Lori J. Wirth, MD, discusses the outcomes of treatment with larotrectinib for patients with NTRK fusion–positive advanced thyroid cancer.

Lori J. Wirth, MD, associate professor of medicine at Harvard Medical School and medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital, discusses the outcomes of treatment with larotrectinib (Vitrakvi) for patients with NTRK fusion–positive advanced thyroid cancer.

Wirth says that advanced thyroid cancer was the most common malignancy in adult patients enrolled in the phase 1 and 2 trials (NCT02576431, NCT02122913, and NCT02637687) investigating larotrectinib in solid tumors with an NTRK1 or NTRK3 fusion. In those with papillary or follicular thyroid cancer, the objective response rate (ORR) was 86% (95% CI, 64%-97%), including some complete responses to larotrectinib. The median progression-free survival (PFS) in these patients was not reached and the 24-month PFS rate was 84% in this population.

However, Wirth notes that in the trials, patients with anaplastic thyroid cancer and an NTRK fusion did not have as high response rates. The ORR of 29% (95% CI, 4%-71%) was still favorable considering the poorer treatment outcomes for patients with advanced anaplastic thyroid cancer, but the responses were also not as durable. The median PFS in this subpopulation was 2.2 months.


0:08 | In patients with advanced thyroid cancer harboring an NTRK1 or NTRK3 fusion, the efficacy of larotrectinib is very good. So in this series of larotrectinib phase 1 and 2 trials, first of all, I think it’s important to note that the diagnosis of thyroid cancer was the most common adult solid tumor diagnosis that was enrolled in the larotrectinib series. So when you’re thinking about NTRK fusion–positive cancers, you definitely want to think about thyroid cancer. But, in the larotrectinib [trial of] patients with thyroid cancer, when patients had papillary thyroid cancer or follicular thyroid cancer, their ORR was 86%. These responses were very durable; in that patient population. The median PFS at the last report still had not yet been reached, but at 24 months, the PFS rate in those patients was 84%. We’re seeing really durable responses, very high response rates, even a small handful of patients achieving a complete response.

1:24 | Unfortunately, in patients in the larotrectinib trials who had NTRK fusion–positive anaplastic thyroid cancer, they did not have responses that were nearly as good as the papillary and follicular thyroid cancer patients. Their ORR was 29%, which doesn’t sound all that bad for anaplastic thyroid cancer, but even when patients did have responses, those responses were very short lived. The median PFS was just 2.2 months in the patients with anaplastic thyroid cancer. So, patients with differentiated thyroid cancer that’s NTRK fusion positive have phenomenal responses, whereas it’s not the case unfortunately, [for patients] with NTRK fusion–positive anaplastic thyroid cancer.

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