Longitudinal health utilities, symptoms and toxicities in patients with ALK- rearranged lung cancer treated with tyrosine kinase inhibitors: a prospective real-world assessment
Abstract
Background: Tyrosine kinase inhibitors (TKIs) have significantly extended survival in patients with ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). While clinical trials typically compare treatments in pairs, real-world data on health utility, symptoms, and toxicities enable broader comparisons across multiple TKIs in this population.
Methods: In a prospective cohort study, outpatients with ALK+ NSCLC treated with various TKIs between 2014 and 2018 were assessed every three months. Data collected included clinical and demographic information, patient-reported symptoms and toxicities, and EQ-5D-derived health utility scores (HUS).
Results: Across 499 encounters involving 76 patients, each TKI maintained stable HUS during periods of disease control—even over extended timeframes. Mean overall HUS per TKI ranged from 0.805 to 0.858, and longitudinal HUS ranged from 0.774 to 0.912, with higher scores observed for second- and third-generation TKIs (alectinib, brigatinib, and lorlatinib). Disease progression corresponded to a mean HUS decline of 0.065 (95% CI: 0.02–0.11). Health utility scores negatively correlated with symptom burden and toxicity (ρ = –0.094 to –0.557). Patients on second- and third-generation TKIs experienced fewer symptoms and toxicities compared to those on crizotinib. In multivariable analysis, only stable disease status and baseline ECOG performance status were significantly associated with improved HUS.
Conclusions: In real-world practice, patients with ALK+ NSCLC maintained stable health utility while on TKIs, provided their disease remained controlled. Among the TKIs studied, alectinib, brigatinib, and lorlatinib demonstrated the most favorable toxicity profiles and highest longitudinal HUS.