OBJECTIVES: Gene fusions involving the neurotrophic tropomyosin-related kinases (NTRK) are a set of biomarkers targeted using tissue agnostic therapy. Because NTRK gene fusions in single tumor types are rare, basket trials are common study designs. With the approval of tissue agnostic drugs- larotrectinib and entrectinib, the feasibility of basket trials has been shown; however, limitations remain. This study aims to identify how alternative studies and study designs have been used to address the limitations of basket trials for rare patient populations treated with tissue agnostic drugs.

METHODS: A targeted literature review (TLR) was conducted to explore the use of real-world data between 2017-2022. The terms "tissue-agnostic therapy," "NTRK," "real world data," "real world evidence," etc. were used yielding technical reports, abstracts, and full-text papers.

RESULTS: A total of 53 publications were identified- 16 meeting the study’s objective were included, consisting of reviews, meta-analyses, concept studies, and real-world evidence (RWE) studies. These studies were typically characterized by- low sample sizes, multiple molecular aberrations, stringent inclusion criteria, presence of selection bias, and the absence of a control arm, making it difficult to generalize their findings to routine clinical practice. Only two RWE studies were found, one assessed treatment patterns using a sample of only 110 NTRK positive patients and evaluated the association between tissue agnostic drug therapy initiation and clinical outcomes. Using the Flatiron Health database, the second study assessed how standard methods of care indirectly compared to NTRK tissue agnostic drug efficacies reported in basket trials, using overall survival as a key clinical outcome.

CONCLUSIONS: Generalization of basket trial results to a real-world setting remains a challenge due to several limitations, including heterogeneity of patient populations and tumor prognosis. Increased utilization of RWE to support basket trial results can help drive a better understanding of treatment decisions for rare patient populations.