Comparative Effectiveness of Alectinib vs. Crizotinib as First-Line Therapy in ALK-Positive Non-Small Cell Lung Cancer: A Real-World Quasi-Experimental Study
Author(s)
Rahul Mudumba, BA, MS1, Xiaofan Liu, MPH2, Jorge J Nieva, MD2, John Romley, PhD2.
1PhD Candidate, University of Southern California, Los Angeles, CA, USA, 2University of Southern California, Los Angeles, CA, USA.
1PhD Candidate, University of Southern California, Los Angeles, CA, USA, 2University of Southern California, Los Angeles, CA, USA.
OBJECTIVES: This retrospective observational cohort study aims to evaluate the real-world comparative effectiveness of alectinib versus crizotinib as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in the United States.
METHODS: Data from Optum’s de-identified Clinformatics® Data Mart Database (2016-2021) were utilized. Patients were identified using ICD-10 codes for lung cancer and ALK TKI pharmacy claims. Eligible patients were ≥18 years of age, with ≥6 months of continuous enrollment prior to treatment initiation. Overall survival (OS) and time-to-treatment discontinuation or death (TTD) were assessed using the Kaplan-Meier method. Cox proportional hazards models were employed to estimate hazard ratios (HRs). To adjust for observed confounding, the primary analysis applied overlap weighting (OW) based on propensity scores estimated via logistic regression incorporating demographic and clinical characteristics; inverse probability treatment weighting (IPTW) served as a robustness check. To address unmeasured confounding, we conducted instrumental variable analysis using a two-stage residual inclusion (2SRI) approach, with index year and geographic region as instruments.
RESULTS: Among 633 eligible patients, 267 received alectinib and 366 received crizotinib. In overlap-weighted Cox models, alectinib was associated with significantly improved OS (HR: 0.60; 95% CI: 0.45-0.79) and TTD (HR: 0.48; 95% CI: 0.38-0.61). IPTW analyses yielded consistent results for OS (HR: 0.65; 95% CI: 0.48-0.87) and TTD (HR: 0.54; 95% CI: 0.43-0.67). In 2SRI models using index year as an instrument, the estimated OS benefit for alectinib (HR: 0.62; 95% CI: 0.34-1.13) remained directionally consistent, but with greater uncertainty.
CONCLUSIONS: To our knowledge, this is the largest real-world comparative effectiveness analysis of first-line targeted therapies for ALK-positive NSCLC and the first to explicitly address unobserved confounding. As crizotinib approaches generic availability and newer agents such as alectinib remain costly, our findings provide timely, policy-relevant evidence to inform value-based treatment decisions for payers and clinicians.
METHODS: Data from Optum’s de-identified Clinformatics® Data Mart Database (2016-2021) were utilized. Patients were identified using ICD-10 codes for lung cancer and ALK TKI pharmacy claims. Eligible patients were ≥18 years of age, with ≥6 months of continuous enrollment prior to treatment initiation. Overall survival (OS) and time-to-treatment discontinuation or death (TTD) were assessed using the Kaplan-Meier method. Cox proportional hazards models were employed to estimate hazard ratios (HRs). To adjust for observed confounding, the primary analysis applied overlap weighting (OW) based on propensity scores estimated via logistic regression incorporating demographic and clinical characteristics; inverse probability treatment weighting (IPTW) served as a robustness check. To address unmeasured confounding, we conducted instrumental variable analysis using a two-stage residual inclusion (2SRI) approach, with index year and geographic region as instruments.
RESULTS: Among 633 eligible patients, 267 received alectinib and 366 received crizotinib. In overlap-weighted Cox models, alectinib was associated with significantly improved OS (HR: 0.60; 95% CI: 0.45-0.79) and TTD (HR: 0.48; 95% CI: 0.38-0.61). IPTW analyses yielded consistent results for OS (HR: 0.65; 95% CI: 0.48-0.87) and TTD (HR: 0.54; 95% CI: 0.43-0.67). In 2SRI models using index year as an instrument, the estimated OS benefit for alectinib (HR: 0.62; 95% CI: 0.34-1.13) remained directionally consistent, but with greater uncertainty.
CONCLUSIONS: To our knowledge, this is the largest real-world comparative effectiveness analysis of first-line targeted therapies for ALK-positive NSCLC and the first to explicitly address unobserved confounding. As crizotinib approaches generic availability and newer agents such as alectinib remain costly, our findings provide timely, policy-relevant evidence to inform value-based treatment decisions for payers and clinicians.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO53
Topic
Clinical Outcomes, Methodological & Statistical Research, Real World Data & Information Systems
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology, Personalized & Precision Medicine, Rare & Orphan Diseases