OBJECTIVES : Determination of ROS1 rearrangements in non-small cell lung cancer (NSCLC) is recommended in guidelines but not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain.

METHODS : A joint model combining a decision-tree with Markov models was developed to determine the cost-effectiveness of testing ROS1 strategy by comparison against a no-ROS1-testing strategy. We assumed that EGFR, ALK and PD-L1 were tested sequentially. Current distribution of ROS1 techniques, testing, positivity, and invalidity rates of biomarker determinations (EGFR, ALK, ROS1, PD-L1) were obtained from experts and Lungpath real-world database. Treatment allocation based on test results was defined by expert opinion. For each treatment, a 3-states partitioned-survival model was developed, where progression-free survival and overall survival curves were extrapolated to model transition of patients among health states at long-term. Only medical direct costs were included (€ 2021). A lifetime horizon was analyzed. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty.

RESULTS : We estimated that 9,578 patients are diagnosed in Spain with advanced non-squamous NSCLC or never-smokers squamous NSCLC in a year. 8,755 of those patients finally tested were defined as the target population entering the model. Over a lifetime horizon, the ROS1-testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1-testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1-testing scenario for the target population. The incremental cost-effectiveness ratio (ICER) was 18,514 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results.

CONCLUSIONS

: Despite the low prevalence of ROS1 rearrangements in NSCLC, which may discourage its determination in some centers, our study shows that ROS1 testing in addition to EGFR and ALK is cost-effective compared to no-ROS1-testing strategy.