Learnings from the Assessments of Entrectinib and Larotrectinib: Health Technology Assessment Challenges Associated with Tumour-Agnostic Therapies

Brogaard, N., Abdul-Ghani, R., Bayle, A.,  Henderson, N.,  Bréant, A, and Steuten, L.

Consulting Report
January 2022

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A paradigm shift is occurring in cancer care with the introduction of tumour-agnostic therapies, for which the indication is defined by the molecular signature of the tumour rather than by its location. Several agents have already gained regulatory approval, including pembrolizumab for solid tumours with high microsatellite instability (MSI-H) or high tumour mutational burden (TMB-H), and larotrectinib and entrectinib for neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours, and many other emerging molecules are set to enter the market over the next decade.

For healthcare systems, one of the biggest challenges lies in the clinical and economic assessment of these therapies, and subsequent decisions regarding reimbursement. As head-to-head data and comparative analyses remain a challenge for tumour-agnostic therapies, clinical evidence provided at the time of regulatory or reimbursement dossier submissions may include indirect comparisons to real-world data (RWD), or intrapatient analyses. In addition, testing costs and value need to be considered, given the need for broad genomic profiling platforms to facilitate patient identification and matching to novel treatments. The evaluation framework of each country’s health technology assessment (HTA) agency determines how these challenges are currently addressed.

This report provides an analysis of HTA agency assessments and reimbursement decisions for entrectinib and larotrectinib across England, Germany, France, Canada, Denmark, Sweden and Scotland. Overall, 13 reimbursement decisions (six for entrectinib, seven for larotrectinib) with publicly accessible documents were analysed to understand the assessment outcomes and what evidence may have influenced them.