OBJECTIVES: Tumour agnostic therapies treat a variety of cancers by targeting a specific genomic feature, regardless of tumour type or location. Two tumour agnostic therapies are regulatory approved in Europe: larotrectinib and entrectinib, both for neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours. This study reviewed health technology assessments (HTAs) conducted for larotrectinib and entrectinib across the EU4 (France, Germany, Italy, Spain) and the UK (England, Scotland).

METHODS: A targeted review of HTA agency websites was conducted on the 12^th April 2024 to identify HTA documentation. The reimbursement outcome, clinical and economic evidence and the HTA body evaluation of the submitted evidence were analysed.

RESULTS: Across the six countries, 11 HTAs were identified (5 larotrectinib, 6 entrectinib). Reimbursement outcomes were positive in 91% of assessments (10/11; 5 non-conditional and non-restrictive [Scotland, Germany and Italy], 4 conditional and non-restrictive [England and Spain], 1 restricted and conditional [France - larotrectinib]) and negative in 9% (1/11 [France – entrectinib]). Key drivers of conditional outcomes included the absence of a trial comparator, immature trial survival data, and because the trial population was not generalisable to clinical practice. Analyses to derive a synthetic comparator arm were submitted in 45% (5/11) of assessments. In 60% (3/5 [France and Germany]) of these assessments, the HTA agency stated they couldn’t assess comparative efficacy due to methodological limitations of the analyses. Where required, a single cost-utility analysis model generating a pooled incremental cost-effectiveness ratio (ICER) across tumour types was submitted (27% [3/11] of assessments). A pooled analysis was accepted in Scotland, while the HTA agency in England stated that the appropriate model structure was uncertain.

CONCLUSIONS: While reimbursement outcomes were predominantly positive, variations in assessment criteria lead to disparities in evidence acceptance and reimbursement outcomes between HTA . Adapted HTA frameworks are required for tumour agnostic therapies to ensure broad and timely patient access.