OBJECTIVES: Larotrectinib is approved for patients with advanced NTRK gene fusion-positive solid tumors. Some studies have demonstrated promising results with larotrectinib compared to systemic therapy. However, a comparison to checkpoint inhibitors such as nivolumab or pembrolizumab has not been done. Our objective was to estimate and compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for patients with non-small cell lung cancer (NSCLC) eligible for larotrectinib vs. patients with unknown NTRK gene fusion status on nivolumab or pembrolizumab. We also looked at patients with metastatic differentiated thyroid cancer (DTC) as pembrolizumab may be considered in certain circumstances.

METHODS: We developed partitioned survival models to project long-term comparative effectiveness of larotrectinib vs. nivolumab or pembrolizumab. Larotrectinib survival data were derived from an updated July 2021 analysis of 21 adult (≥18 years of age) patients with metastatic NTRK gene fusion-positive NSCLC and 21 with metastatic DTC from the clinical trials program (NCT02122913, NCT02637687, and NCT02576431). Survival inputs for nivolumab were derived from NCT01673867 for NSCLC. For pembrolizumab, inputs were from NCT01905657 for NSCLC, and NCT02054806 for DTC. Progression free and overall survival were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Log-normal) fit to available data. Exponential fits were chosen based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the pre progression and post progression health states by utility values.

RESULTS: In NSCLC, larotrectinib resulted in gains of 5.87 and 5.74 LYs compared to nivolumab and pembrolizumab, respectively, which translated to gains of 3.53 and 3.55 QALYs. In DTC, larotrectinib resulted in a gain of 2.22 LYs and 2.69 QALYs compared to pembrolizumab.

CONCLUSIONS: In metastatic NSCLC and DTC, larotrectinib may produce substantial life expectancy and quality-adjusted life-year gains compared to immune checkpoint inhibitors. Additional data with longer follow-up will further inform this comparison.