Insights About NTRK Gene Fusion Testing and TRK Inhibitors Comparative Effectiveness for Best Clinical Practice

Abstract

Precision medicine aims to identify the genetic landscapes of each patient's cancer to maximize effectiveness and minimize toxicity to normal cells. Due to the efficacy of tropomyosin receptor kinase (TRK) inhibitor therapy, it is currently clinically recommended to identify patients with neurotrophic tropomyosin receptor kinase (NTRK) fusion-driven cancer. In this article we aim to provide perceptions to enhance best clinical practices about NTRK gene fusion testing and monitoring parameters for the approved TRK inhibitors as well as its comparative effectiveness based on previously published articles and guidelines. Identification of NTRK gene fusion may be attained using different methods based on histology and molecular findings. The possible methods for detection are immunohistochemistry, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction and next generation sequencing. FDA approved two TRK inhibitors Larotrectinib and Entrectinib. Based on management guidelines, oncologists have one opportunity to decide which TRK inhibitor to choose for patients. There is no direct comparison in clinical trials and Larotrectinib versus Entrectinib comparative efficacy still unclear. In addition, cross-trial comparisons are susceptible to potential biases. Indirect comparative efficacy of Larotrectinib (Vitrakvi) versus Entrectinib (Rozlytrek) was conducted by Jesus Garcia-Foncillas and colleagues. The matching-adjusted indirect comparison (MAIC) to compare the 2 agents was utilized. They assumed this model would aid to balance baseline characteristics and facilitate cross-trial comparisons. The published findings propose favorable efficacy for Larotrectinib in regard to OS and PFS and comparable ORR and safety profiles compared to Entrectinib in treating TRK fusion positive cancer. In conclusion, further research should re-assess the comparative effectiveness of both TRK inhibitors as long-term survival data mature and increased number of patients are treated. Furthermore, data with longer follow up times will further enlighten this comparison.