OBJECTIVES: Larotrectinib is FDA-approved for neurotrophic receptor tyrosine kinase gene fusion (NTRK) positive, locally advanced or metastatic, progressive, thyroid cancer. Sorafenib and lenvatinib are approved for locally advanced or metastatic differentiated thyroid carcinoma refractory to radioactive iodine treatment. Our objective was to compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for NTRK-positive thyroid cancer patients eligible to receive larotrectinib, sorafenib, or lenvatinib.

METHODS: We developed a partitioned survival model to project long-term comparative effectiveness of larotrectinib vs. sorafenib or lenvatinib. Larotrectinib survival data, assessed by independent review committee, were derived from 23 NTRK+ metastatic thyroid cancer patients (including both anaplastic and differentiated thyroid cancer patients) from the larotrectinib clinical trials program. Survival inputs for sorafenib and lenvatinib were derived from published randomized Phase III clinical trials. Progression free (PFS) and overall survival (OS) for all treatments was estimated using parametric curve fits (Weibull, Exponential, Log-Logistic, and Log-normal). Exponential fits were used based on goodness-of-fit and clinical plausibility. QALYs were estimated by applying pre-progression and post-progression health state utilities derived from literature. In a scenario analysis, we adjusted sorafenib and lenvatinib survival to a NTRK+ population using a prognostic hazard ratio adjustment based on a recent flatiron data analysis. Model uncertainty was evaluated using one-way and probabilistic sensitivity analysis (PSA).

RESULTS: Treatment with larotrectinib yielded 6.42 LYs and 4.03 QALYs. Compared with lenvatinib and sorafenib, this provided an additional 2.06 and 0.95 LYs and an additional 1.12 and 0.88 QALYs, respectively. Adjusting for NTRK prognosis, the incremental LY’s (QALYs) for sorafenib and lenvatinib increased further to 3.26 (1.93) and 2.41(1.73), respectively.

CONCLUSIONS: Larotrectinib is estimated to be superior to sorafenib and lenvatinib in eligible advanced thyroid cancer patients. Our analysis was limited by lack of NTRK-specific data on sorafenib and lenvatinib, small sample sizes, and the naïve direct (cross-trial) comparison.