Larotrectinib demonstrates durable response and safety in TRK fusion thyroid cancer

A new analysis of larotrectinib in patients with TRK fusion thyroid cancer shows compelling efficacy and safety data, including a high durable response rate and a manageable safety profile.

Among the 31 patients included in the analysis, the overall response rate (ORR) was 65% (95% CI, 45%-81%), including 3 cases (10%) complete response, 17 cases (55%) partial response (PR), 5 cases (16%) stable disease (SD), 4 cases (13%) progressive disease (PD), and 2 cases (6%) unevaluable. The ORR was 79% (95% CI, 58%-93%) in patients with differentiated thyroid cancer (DTC) and 14% (95%, CI 0%-58%) in patients with anaplastic thyroid cancer (ATC). The median time to response for all patients was 1.9 months (range, 1.6-16.2), and the median duration of treatment was 31 months (range, 1-88).

The median duration of response was 35 months (95% CI, 19 not estimable [NE]), progression-free survival was 39 months (95% CI, 17-NE), and the median follow-up times were 48, 42, and 68 months, respectively, and overall survival (OS) was not reached (95% CI 28-NE). For patients with DTC, the median OS was not reached (95% CI, 56-NE), and for patients with ATC, the median OS was 9 months (95% CI, 3-NE). At 6 years, the OS rate for all patients was 60% (95% CI, 41%-79%), compared with 71% (95% CI: 50%-91%) for DTC patients and 17% (95% CI: 0%-46%) for ATC patients.

Treatment-related adverse events (TRAEs) were primarily grade 1 to 2, with grade 3 to 4 TRAEs reported in 5 (16%) patients, including weight gain in 2 patients, anemia, decreased lymphocyte count, and hepatolysis in 1 patient each. No patients discontinued treatment due to TRAEs.

Larotinib showed rapid and durable response, prolonged survival and good safety in patients with TRK fusion DTC This latest analysis builds on the established understanding of TRK fusions and the role of larotrectinib. TRK fusions are known oncogenic drivers in various solid tumors, including a subset of thyroid cancers. Larotrectinib is a highly selective and CNS-active TRK inhibitor approved for adult and pediatric patients with solid tumors harboring NTRK gene fusions. Previous data have consistently demonstrated the efficacy and safety of larotrectinib in patients with TRK fusion solid tumors, including those affecting the thyroid gland.

This latest analysis aims to further understand the performance of larotrectinib inTRK fusion thyroid cancer patients and consolidate its status as an important treatment method for oncologists. Patients with TRK fusion thyroid cancer were included in the analysis. These patients were enrolled in 1 of 3 clinical trials evaluating larotrectinib (NCT02576431, NCT02122913, NCT02637687).

Larotinib was administered at a dose of100 mg twice daily (BID) in adults; 2 pediatric patients received 100 mg/m2 BID (maximum dose 100 mg BID). Response was assessed by an independent review committee (IRC) according to RECIST v1.1, with ORR as the primary endpoint. Secondary endpoints are DOR, PFS, OS and safety.

At the data cutoff date of July 2024, a total of 31 patients were enrolled, including 24 (77%) DTC patients and 7 (23%) ATC patients. The median age of patients was 60 years (range 6-80), the majority of patients were female (71%), and the median time since initial cancer diagnosis was 5 years (range 0-46). In the metastatic/unresectable setting, a total of 17 (55%) patients did not receive systemic therapy. Six (19%) patients received at least 2 treatments, and 24 (77%) patients received radioactive iodine therapy. All NTRK gene fusions were identified by next-generation sequencing. At the time of data cutoff, 7 (23%) patients were still receiving treatment, and 5 of these patients had their disease under control.

These results suggest that larotrectinib is an effective treatment option for patients with TRK fusion [thyroid cancer]. Testing patients for NTRK gene fusions is important for early identification of patients who may benefit from this precise treatment.

Reference materials:https://www.targetedonc.com/view/larotrectinib-shows-durable-responses-safety-in-trk-fusion-thyroid-carcinoma