Clinical and economic impact of current ALK rearrangement testing in Spain compared with a hypothetical no-testing scenario

Abstract

Background Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. Methods A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. Results We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. Conclusions ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain.

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

“…In line with the previous model developed by Nadal et al [ 23 ], a joint model combining a decision-tree with Markov models was developed to determine long-term health results and associated costs of patients with NSCLC, but in this case by comparing a testing ROS1 strategy by comparison against a no-ROS1 testing strategy in Spain, using Microsoft Excel (Fig. 1 ).…”

“…The definition of the target population was similar to the one used in the previous model developed by Nadal et al (2021) [ 23 ]. A hypothetical cohort of patients with advanced or metastatic NSCLC, who were ‘theoretical’ candidates for the molecular diagnosis, was initially estimated.…”

“…To establish the transition of the hypothetical cohort between the health states of the Markov models and given that the time horizon of the analysis (lifetime) is longer than the observation periods of the clinical trials, it is necessary to extrapolate the Kaplan-Meier curves of PFS and OS to the long term. In the absence of individualized data for all treatments to explore different parametric distributions, the panel of experts assumed, in line with the previous model developed, the exponential models based on the median PFS and OS reported in the respective studies [ 23 ].…”

“…In this regard, the expert panel agreed to keep the same assumptions made in the previous model developed. Thus, it was considered that most patients will have shown progression at the first follow-up visit and that all of them will have progressed at the second visit, assuming a median PFS of 2 months (considering that no patient exceeds 6 months of treatment -stop rule-) and a median OS of 18 months [ 23 ].…”

“…Based on the clinical implications of ROS1 fusion detection in NSCLC patients, it is crucial to accurately identify ROS1 alterations while minimizing response time [ 1 , 22 ]. The importance of testing for other biomarkers, such as ALK , has already been quantified in Spain by Nadal et al [ 23 ], however, it has not been quantified for the determination of a less prevalent biomarker such as ROS1 . For this reason, the main objective of this analysis was to quantify the clinical and economic impact of ROS1 determination in patients with advanced NSCLC in Spain, comparing a testing ROS1 strategy with sequentially testing ROS1 in addition to EGFR and ALK versus a no-testing ROS1 strategy.…”