OBJECTIVES: Larotrectinib and entrectinib are tumor-agnostic tropomyosin receptor kinase (TRK) inhibitors for the treatment of advanced or metastatic solid tumor cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. Regulatory approval of both agents was based on data from single-arm Phase 1/2 studies, including tumor-agnostic basket trials. In the absence of randomized controlled trials, there remains a paucity of data to demonstrate the comparative effectiveness of these agents. The objective was to extrapolate clinical trial results to compare estimated progression-free and overall life-years (LYs) and quality-adjusted LYs (QALYs) for larotrectinib and entrectinib in patients with colorectal cancer (CRC), soft tissue sarcoma (STS), and brain metastases (BM) at baseline.

METHODS: We performed a naïve direct comparison of larotrectinib versus entrectinib using a partitioned survival model to project long-term progression free and overall survival. Larotrectinib survival data were from a July 2020 analysis of adult patients (≥18 years of age) with NTRK fusion CRC, STS, and BM prior to starting TRK inhibitor treatment. Survival inputs for entrectinib were derived from published literature and conference abstracts. Exponential curve fitting methods were used to extrapolate progression-free (PFS) and overall survival (OS) for both treatments and across all three tumor types.

RESULTS: Larotrectinib resulted in an additional 1.58 LYs (1.17 QALYs), 5.81 LYs (2.02 QALYs), and 1.01 LYs in CRC, STS, and BM, respectively as compared to entrectinib. These analyses that included more patients and more mature data from the pivotal Phase 1/2 studies showed consistent results for patients treated with larotrectinib as compared to entrectinib.

CONCLUSIONS: In patients with NTRK gene fusion CRC, STS, and BM, larotrectinib provided life expectancy and QALY gains compared to entrectinib. Additional studies would be beneficial as more patients are treated and survival data develops to better inform comparative effectiveness and economic models.