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. 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. 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. 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.
Li et al. (2026) studied this question.