Arterial and Venous Thromboembolism in ALK-Rearrangement-Positive Non-small Cell Lung Cancer: A Population-Based Cohort Study

• Published in: The oncologist (Dayton, Ohio) Ohio), 2023-06, Vol.28 (6), p.e391-e396
• Main Authors: Icht, Oded, Leader, Avi, Batat, Erez, Yosef, Lilach, Shochat, Tzippy, Goldstein, Daniel A, Dudnik, Elizabeth, Spectre, Galia, Raanani, Pia, Hammerman, Ariel, Zer, Alona
• Format: Article
• Language: English
• Subjects: Anticoagulants - therapeutic use; Carcinoma, Non-Small-Cell Lung - complications; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Cohort Studies; Complications and side effects; Demographic aspects; Development and progression; Diagnosis; Humans; Lung Cancer; Lung cancer, Non-small cell; Lung Neoplasms - complications; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Protein Kinase Inhibitors - therapeutic use; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Risk factors; Thromboembolism; Venous Thromboembolism - etiology; Venous Thromboembolism - genetics
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyad061

Abstract Introduction There is scarce data regarding the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in the molecular subtypes of non-small cell lung cancer (NSCLC). We aimed to investigate the association between Anaplastic Lymphoma Kinase (ALK)-positive NSCLC and thromboembolic events. Methods A retrospective population-based cohort study of the Clalit Health Services database, included patients with NSCLC diagnosed between 2012 and 2019. Patients exposed to ALK-tyrosine-kinase inhibitors (TKIs) were defined as ALK-positive. The outcome was VTE (at any site) or ATE (stroke or myocardial infarction) 6 months prior to the diagnosis of cancer, until 5 years post-diagnosis. The cumulative incidence of VTE and ATE and hazard-ratios (HR) with 95% CIs were calculated (at 6- 12- 24 and 60-months), using death as a competing risk. Cox proportional hazards multivariate regression was performed, with the Fine and Gray correction for competing risks. Results The study included 4762 patients, of which 155 (3.2%) were ALK-positive. The overall 5-year VTE incidence was 15.7% (95% CI, 14.7-16.6%). ALK-positive patients had a higher VTE risk compared to ALK-negative patients (HR 1.87 [95% CI, 1.31-2.68]) and a 12-month VTE incidence of 17.7% (13.9-22.7%) compared to 9.9% (9.1-10.9%) in ALK-negative patients. The overall 5-year ATE incidence was 7.6% [6.8-8.6%]. ALK positivity was not associated with ATE incidence (HR 1.24 [0.62-2.47]). Conclusions In this study, we observed a higher VTE risk, but not ATE risk, in patients with ALK-rearranged NSCLC relative to those without ALK rearrangement. Prospective studies are warranted to evaluate thromboprophylaxis in ALK-positive NSCLC. There is scarce data regarding the incidence of venous thromboembolism and arterial thromboembolism in the molecular subtypes of non-small cell lung cancer (NSCLC). This study investigated the association between ALK-positive NSCLC and thromboembolic events.