OBJECTIVES : Better understanding of oncogenic signaling processes and subsequent therapy targeting specific alterations represent the real frontline of cancer treatment; entrectinib is a new inhibitor of the tyrosine kinases (TKI) encoded by the gene ROS1. An international AUC model has been adapted to Italian clinical practice in order to estimate its cost-utility in the treatment of ROS1+ NSCLC, with respect to crizotinib, currently TKI approved in Italy.

METHODS : Main clinical drivers are PFS and OS curves, estimated by parametric extrapolation to observed data from the pooled entrectinib trials; given the lack of head-to-head studies, a Matched Adjusted Indirect Comparison has been carried out to estimate hazard ratios vs. crizotinib. Utilities are taken from STARTRK-2 data, valued with Italian tariffs. Economical inputs concern oral drug cost, without administration (both competitors), adverse events management, and supportive care; unit costs are based on national literature data and current tariffs, from NHS perspective. Drugs are costed based on protocol/label planned dose, observed length of treatment and parity price assumption.

RESULTS : Lifetime model results estimated that entrectinib, when compared to crizotinib, induces a survival gain of 2.17 life years in the post-progression phase, corresponding to 1.39 QALYs. The associated cost increase of 117K €, mainly due to the improvement of life expectancy (paradox effect) and to longer TKI treatment duration, leads to an ICER of 54 K€/LY and to an ICUR around 80 K€/QALY.

CONCLUSIONS : Entrectinib increases expected survival in ROS1+ NSCLC patients with an incremental cost-utility that can be considered acceptable, especially considering the approximation of ROS1-NSCLC to a rare disease. Main limitations are the ineluctable indirect comparison approach, that together with the poor knowledge on the natural history of the ROS1-NSCLC population make the analysis subject to considerable uncertainty.