Longitudinal Health Utilities, Symptoms and Toxicities in Patients with ALK-Rearranged Lung Cancer Treated with Tyrosine Kinase Inhibitors: A Prospective Real-World Assessment

Background: Tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). Clinical trial data can generally compare drugs in a pair-wise fashion. Real-world collection of health utility data, symptoms, and toxicities allows for the direct comparison between multiple TKI therapies in the population with ALK+ NSCLC. Methods: In a prospective cohort study, outpatients with ALK+ recruited between 2014 and 2018, treated with a variety of TKIs, were assessed every 3 months for clinico-demographic, patient-reported symptom and toxicity data and EQ-5D-derived health utility scores (HUS). Results: In 499 longitudinal encounters of 76 patients with ALK+ NSCLC, each TKI had stable longitudinal HUS when disease was controlled, even after months to years: the mean overall HUS for each TKI ranged from 0.805 to 0.858, and longitudinally from 0.774 to 0.912, with higher values associated with second- or third-generation TKIs of alectinib, brigatinib, and lorlatinib. Disease progression was associated with a mean HUS decrease of 0.065 (95% confidence interval: 0.02 to 0.11). Health utility scores were inversely correlated to multiple symptoms or toxicities: rho values ranged from −0.094 to −0.557. Fewer symptoms and toxicities were associated with the second- and third-generation TKIs compared with crizotinib. In multivariable analysis, only stable disease state and baseline Eastern Cooperative Oncology Group performance status were associated with improved HUS. Conclusions: There was no significant decrease in HUS when patients with ALK+ disease were treated longitudinally with each TKI, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean HUS longitudinally in the real-world setting.