Treatment Pathways, Drug Utilization and Healthcare Resource Consumption in Patients with Metastatic Anaplastic Lymphoma Kinase-Positive Non-small Cell Lung Cancer: A Real-World Analysis with Administrative Databases in Italy

Abstract

Background: Metastatic anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) is a rare but clinically distinct subtype of lung cancer with therapeutic sensitivity to ALK inhibitors (ALKi). Over the past decade, several ALKi have been introduced in Italy, yet real-world data on their utilization, patient characteristics, outcomes, and healthcare burden remain limited. Objectives: This study aimed to characterize Italian patients with ALK+ Metastatic non-small cell lung cancer (mNSCLC) treated with ALKi, examining treatment patterns, time to next treatment (TTNT), overall survival (OS), and healthcare resource utilization (HCRU) and associated costs. Methods: An observational retrospective analysis was conducted using administrative databases from Italian Local Health Units (LHUs), covering approximately 6.5 million individuals between January 2010 and June 2024. Patients with ALK+ mNSCLC treated with ALKi from 2020 onward were included. Patient demographics, treatment sequences, TTNT, OS, HCRU, and costs were analyzed using Kaplan-Meier estimates, Cox regression, and generalized linear models. Results: Among 29,418 mNSCLC patients identified, 274 received ALKi. Alectinib was the most used first-line ALKi (67.2%), followed by crizotinib (18.2%), brigatinib (6.9%), and chemotherapy plus ALKi (5.8%). Alectinib demonstrated the longest median TTNT (42.6 months) and OS (43.2 months). Treatment switch and mortality were not significantly associated with therapy type, age, sex, or comorbidity, except for increased mortality risk in patients’ ≥ 80 years. Over six months, brigatinib incurred the lowest total healthcare costs (€12,943) and no hospitalizations, while alectinib had the highest costs (€29,115), primarily due to drug expenditures. Conclusions: This real-world study highlights evolving treatment patterns in ALK+ mNSCLC, with increasing use of next-generation ALKi. Alectinib remains the most prescribed first-line option with favorable outcomes, albeit with higher costs. Brigatinib demonstrated lower healthcare utilization and cost, supporting its potential cost-effectiveness. These findings emphasize the need for continued real-world evaluation to optimize care and resource allocation in ALK+ mNSCLC.