Clinical and economic impact of ‘ROS1-testing’ strategy compared to a ‘no-ROS1-testing’ strategy in advanced NSCLC in Spain

Abstract

Background Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is 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 (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. Results A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered 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. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. Conclusions Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

A Real-World Experience from a Single Center (LPCE, Nice, France) Highlights the Urgent Need to Abandon Immunohistochemistry for ROS1 Rearrangement Screening of Advanced Non-Squamous Non-Small Cell Lung Cancer

“…However, a number of restrictions can limit the possibility of developing, in daily practice, the new algorithm described above. First, in contrast to immunohistochemical platforms that are largely available in the majority of pathology laboratories, NGS approaches are not equally distributed in all countries or even in organizations and institutions in a single country [ 35 , 36 ]. Second, even if available, access to some NGS approaches could be limited, due to the cost and absence of reimbursement of costs, and can also be associated with a long TAT to obtain the results, which is not compatible with international guidelines [ 15 ].…”

“…Second, even if available, access to some NGS approaches could be limited, due to the cost and absence of reimbursement of costs, and can also be associated with a long TAT to obtain the results, which is not compatible with international guidelines [ 15 ]. Due to the lower cost and the shorter TAT, IHC and/or rapid RT-PCR can be easily performed as an alternative for ROS1 status assessment [ 16 , 36 , 37 , 38 ]. More importantly, IHC and FISH methods can sometimes be the only approaches that detect some therapeutic targets in very small tissue biopsies and/or, if only a low percentage of tumor cells are present, knowing that NGS can lead to some false negative results due to the low quantity and/or quality of the extracted nucleic acid [ 39 , 40 ].…”

Cost-Effectiveness of Next-Generation Sequencing Versus Single-Gene Testing for the Molecular Diagnosis of Patients With Metastatic Non–Small-Cell Lung Cancer From the Perspective of Spanish Reference Centers

“…In the absence of individualized patient data for all treatments, it was considered to fit exponential models to lambda parameters obtained from median PFS and OS (Table S5, Data Supplement), in line with previous studies. 11 , 27 , 28 Therefore, cost and utilities are assigned to PSM health states, and the proportion of patients in each state is estimated using exponential PFS and OS curves.…”

Diagnostic Approach of Lung Cancer: A Literature Review

“…48 Even though the prevalence of ROS1 rearrangement is relatively low, detection of this genetic alteration can lead to specific treatment using entrectinib or crizotinib to improve life expectancy. 49 BRAF, MET, RET, and HER2 testing is not recommended if the result of routine EGFR, ALK, and ROS1 testing is negative. However, it is appropriate to perform KRAS as part of larger testing panels either initially or when the result of EGFR, ALK, and ROS1 testing is negative.…”