The value of targeted therapies in non-small-cell lung cancer

Le résumé fourni par la source

Lung cancer is the leading cause of cancer-related mortality worldwide, with 80–90% of patients diagnosed with non-small-cell lung cancer (NSCLC). Over the past decade, treatment for advanced NSCLC has evolved from chemotherapy to personalized therapies targeting specific molecular alterations, including ALK, EGFR, ROS1, and PD-(L)1. While these therapies have improved survival outcomes, they also place increasing pressure on healthcare budgets. The first part of this thesis evaluated the health economic value of targeted therapies through a review of NICE technology appraisals and the methodological use of utility values in QALY estimation. NSCLC appraisals became increasingly complex, incorporating multiple indications, subpopulations, and comparators. Although most therapies received positive reimbursement recommendations, substantial variation was observed in the selection and application of utility values. Furthermore, age-specific analyses were absent despite mutation-driven NSCLC increasingly affecting younger patients, highlighting an opportunity to better reflect differences in long-term outcomes and societal impact. The second part assessed the value of targeted therapies through cost-effectiveness and budget impact analyses. A cost-utility analysis found a low probability that first-line lorlatinib would be cost-effective compared with crizotinib or alectinib in untreated ALK-positive NSCLC. In contrast, a budget impact analysis demonstrated that first-line afatinib followed by osimertinib resulted in lower costs and improved long-term outcomes compared with first-line osimertinib followed by chemotherapy in EGFR-mutated NSCLC. A complementary case study showed that nintedanib was cost-effective for progressive fibrosing interstitial lung disease, a condition relevant to NSCLC as both a comorbidity and treatment-related adverse event. Overall, the thesis supports a holistic, sequence-based approach to economic evaluation that incorporates quality of life, long-term adverse events, and age-specific considerations.

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