Comparative effectiveness and cost-effectiveness of ALK-positive NSCLC sequential strategies under physician and patient preferences

BACKGROUND: Although advances in multi-line cancer treatment have improved patient survival outcomes, they have also introduced significant economic and resource-allocation challenges. The ultimate survival outcome depends on the cumulative effect of all treatment lines and is significantly influenced by physician and patient preference​. Given the predominant focus of pharmacoeconomic evaluations in China on single-line treatments, further research that integrates high-quality clinical evidence with stakeholder preferences is necessary to evaluate sequential strategies. METHODS: A systematic search of PubMed, Embase, and ClinicalTrials.gov identified relevant clinical trials for advanced ALK-positive non-small-cell lung cancer (NSCLC). A semi-Markov model was applied to evaluate the effectiveness and cost-effectiveness of sequential strategies from the Chinese healthcare system perspective. The primary effectiveness outcomes measured were median overall survival (OS) and quality-adjusted life years (QALYs), and cost-effectiveness was assessed based on net monetary benefit (NMB). Health state utilities and costs were sourced from published literature, publicly available national databases. Additionally, we employed a discrete choice experiment (DCE) to quantify advanced NSCLC patients' preferences for treatment attributes. These preference weights were then integrated with the performance of ​​sequential strategies​​ to calculate the selection probabilities. RESULTS: A total of 27 RCTs were included, informing 35 sequential strategies. The highest effectiveness were observed in ​​third-generation ALK-TKI lorlatinib-initiated regimens​​, particularly with the ​​lorlatinib-to-alectinib​​ sequence achieving ​​8.4 QALYs​​. At a willingness to pay(WTP) threshold of $ 25,799, the Che + Che+BSC regimen yielded the highest NMB ($16,180). Derived from the DCE, patient preference weights identified progression-free survival (PFS) as the most important attribute (40.9%). The alectinib-to-ensartinib sequential strategy demonstrated the highest selection probability in physician-patient preferences. CONCLUSIONS: According to current analyses, although treatment initiating with the third-generation ALK-TKI led in effectiveness, chemotherapy-dominated sequential treatment remained the most cost-effective option when costs were considered. Our study identified a strong physician-patient alignment on preference priorities for treatment pathway selection, placing greater weight on the efficacy dimension, which was reflected in the high preference for sequential second- and third-generation ALK-TKI strategies. These findings underscore the importance of strategic ALK-TKI sequencing and ​​advocate for​​ shared decision-making.