Comparing the Long-Term Effectiveness of Larotrectinib Versus Entrectinib

The standard treatment for soft tissues sarcomas (STS) has been the combination of an anthracycline, such as doxorubicin, and an alkylating agent, such as ifosfamide. In a study presented at AMCP 2022, researchers aimed to compare the long-term effectiveness of larotrectinib and entrectinib in treating the subpopulation of patients with STS with neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Based on their data, lead author, K. Suh and colleagues concluded that, “in metastatic TRK fusions STS, larotrectinib may produce substantial life expectancy and quality-adjusted life-year gains compared to entrectinib.”

The investigators designed a “partitioned survival model” to estimate the life years (LYs) and quality-adjusted life-years (QALYs) of patients with TRK fusions STS receiving either larotrectinib or entrectinib. The authors noted that some data required extrapolation, as the dataset had less than three years of follow-up for both drugs at data cutoff. Survival data for larotrectinib included 23 patients with TRK fusion STS, while entrectinib survival inputs were based on 16 patients. Both groups were derived from clinical trials on the drugs. In addition to LYs and QALYs, progression-free survival (PFS), and overall survival (OS) outcomes were compared.

According to the poster, the estimated pre-progression survival for patients who received larotrectinib was 2.08 LYs (1.03 QALYs) compared to 0.66 LYs (QALYs) for those who received entrectinib. “In total, larotrectinib resulted in 7.00 LYs and 2.51 QALYs compared to 1.26 LYs and 0.51 QALYs for entrectinib.” Based on these figures and their other estimates, the authors reported that larotrectinib yielded additional gains of 5.74 LYs and 2.00 QALYs versus entrectinib.

Between larotrectinib and entrectinib, the only two drugs currently approved for this subpopulation of TRK fusion STSs, Suh and colleagues found that larotrectinib appeared to yield greater improvements in patient survival outcomes. The authors did acknowledge that “additional data with longer follow-up times will further inform this comparison.”