Impact of ALK Rearrangement on Venous and Arterial Thrombotic Risk in Non-Small Cell Lung Cancer

Lung Cancer

Al-Samkari H, et al. J Thorac Oncol 2020.


INTRODUCTION: Clinical venous thromboembolism (VTE) risk prediction scores, such as the Khorana Risk Score, perform poorly in non-small cell lung cancer (NSCLC), possibly because tumor molecular subtype is omitted. Prior studies suggest a possible increased VTE risk in ALK-rearranged NSCLC, but data are conflicting.

METHODS: We performed a retrospective cohort study of advanced-stage NSCLC patients diagnosed between 2009 and 2019. Multivariable time-to-event analyses modeling risk of first venous or arterial thrombosis in ALK and non-ALK NSCLC groups controlling for covariates known to impact thrombosis risk (15 in VTE model and 17 in arterial thrombosis model) were performed using Cox proportional hazards regression and competing-risks regression. Multivariable negative binomial regression modeled total VTE rate.

RESULTS: 422 ALK-rearranged and 385 non-ALK-rearranged NSCLC patients were included. ALK patients were younger, had better performance status and lower rates of most thrombotic risk factors but had significantly higher rates of initial VTE (42.7% vs. 28.6%), recurrent VTE (13.5% vs. 3.1%) and similar rates of arterial thrombosis (5.0% vs. 4.4%) than non-ALK NSCLC. VTE risk attributable to ALK was significant [Cox model: HR 3.70 (95% CI, 2.51-5.44, P<0.001); competing-risks: SHR 3.91 (95% CI, 2.55-5.99, P<0.001)]. Negative binomial modeling demonstrated higher VTE rates in ALK patients [IRR 2.47 (95% CI, 1.72-3.55, P<0.001)]. OR for recurrent VTE was 4.85 (95% CI 2.60 to 9.52, P<0.001). Arterial thrombosis risk attributable to ALK was significant [Cox model: HR 3.15 (95% CI, 1.18-8.37, P=0.021); competing-risks: SHR 2.80 (95% CI, 1.06-7.43, P=0.038)].

CONCLUSIONS: In time-to-event analyses controlling for thrombosis risk factors, the ALK rearrangement conferred a 4-fold increase in VTE risk and 3-fold increase in arterial thrombosis risk in NSCLC. These patients may benefit from pharmacologic thromboprophylaxis.