OBJECTIVES : New clinical cut-off data are used to update the incremental cost-utility ratio (ICUR) of entrectinib versus standard of care (SOC) in various solid tumor types with NTRK rearrangements. An international, lifetime, 3-health states, partitioned survival model is adapted to the Italian National Health Service (NHS) perspective.

METHODS : Progression-free survival (PFS) and overall survival (OS) curves define proportions of patients within each health state at each time point. For entrectinib, PFS and OS are modelled by fitting parametric distributions on empirical data from pooled trials. Given the lack of head-to-head studies, median values of PFS and OS are used to estimate the mean values for SOC by exponential extrapolation. A minor population adjustment is performed weighting the mean PFSs and OSs for tumor type by the frequencies observed in the pooled entrectinib NTRK+ subgroups. New utilities for progression-free state are taken from STARTRK-2 EQ5D-3L data on 74-patients, weighted by Italian tariffs, whereas literature data are used for post-progression state. Economical inputs concern drug acquisition and administration, adverse events management, and supportive care; unit costs, expressed in Euro-2019, are based on national literature data and current tariffs. Deterministic and probabilistic sensitivity analyses assess the impact of variables uncertainty.

RESULTS : In NTRK tumor agnostic indication, entrectinib generates incremental QALYs (0.93) and costs (€85K) compared to SOC. Expected ICUR is about €90K per QALY gained. Entrectinib cost is the parameter that mostly influences final ICUR. Values from PSA are uniformly distributed around base case value.

CONCLUSIONS : Entrectinib is a potent targeted inhibitor of NTRK-kinases expressed in different tumor types and it brings to clinical benefits in patients harboring NTRK-rearrangements. The present analysis is characterized by uncertainty and further analysis of survival data is warranted: main limitations are the ineluctable naïve-indirect comparison approach and poor knowledge on the natural history of the NTRK+ population.