Risk of thromboembolism in patients with ALK- and EGFR-mutant lung cancer: A cohort study

Joanna Roopkumar, Shyam K Poudel, Lorenzo Gervaso, Chandana A Reddy, Vamsidhar Velcheti, Nathan A Pennell, Keith R McCrae, Alok A Khorana, Joanna Roopkumar, Shyam K Poudel, Lorenzo Gervaso, Chandana A Reddy, Vamsidhar Velcheti, Nathan A Pennell, Keith R McCrae, Alok A Khorana

Abstract

Introduction: Thromboembolism (TE) is common in patients with non-small cell lung cancer (NSCLC) and is associated with worse outcomes. Recent advances in the understanding of NSCLC have led to the identification of molecular subtypes such as anaplastic lymphocyte kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. The association of these subtypes with risk of TE has not been fully explored.

Methods: We conducted a retrospective cohort study of consecutive NSCLC patients seen at the Cleveland Clinic from July 2002 through July 2017 for whom molecular classification and follow-up were available. TE events included deep vein thrombosis (DVT), pulmonary embolism (PE), visceral vein thrombosis (VVT), and arterial events. TE-free survival and overall survival rates for each of the molecular subtypes (wild-type, ALK-mutant, and EGFR-mutant) were estimated by the Kaplan-Meier method. Cox proportional hazard regression analysis was used to identify factors associated with the endpoints TE and overall survival. TE was analyzed as a conditional, time-dependent covariate to assess its impact with respect to overall survival.

Results: The study population consisted of 461 patients. Approximately half were females (n = 263, 57%) and 58% (n = 270) were older than 65 years. TE occurred in 98 of 461 patients (21.3%) during a median follow-up of 33.1 months. The highest cumulative rates of TE were observed in patients with ALK-mutant NSCLC (N = 20/46, 43.5%) followed by patients with EGFR-mutant cancers (N = 35/165, 21.2%) and wild-type cancers (N = 43/250, 17.2%) P < .05. Cumulative incidence of TE at 6 months of follow-up was 15.7% (95% confidence interval [CI]: 5.0%-26.4%) for ALK-mutant cancers, 8.8% (95% CI: 4.4%-13.2%) for EGFR-mutant cancers, and 9.2% (95% CI: 5.4%-12.9%) for wild-type cancers. Patients who experienced TE had worse overall survival (all patients: hazard ratio = 2.8 95% CI 2.1-3.6, P < .001).

Conclusions: Patients with ALK-mutant advanced lung adenocarcinoma have the highest rate of TE. TE is associated with worse survival across molecular subtypes. These findings should be taken into consideration in decision-making regarding thromboprophylaxis.

Keywords: anaplastic lymphocyte kinase; epidermal growth factor receptor; molecular subtyping; non-small cell lung cancer; thromboembolism.

© 2020 International Society on Thrombosis and Haemostasis.

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