The rate of venous thromboembolism in patients with non-small cell lung cancer treated with chemotherapy or check point inhibitors.

Abstract

e21053 Background: Treatment with immune checkpoint inhibitors (CPI) targeting PD-1 or PD-L1 significantly improves progression free survival and overall survival in patients with non-small cell lung cancer (NSCLC). Emerging literature suggests that the proinflammatory state of CPIs may increase the risk of thromboembolism, both venous (VTE) and arterial (ATE), which is of great concern as thromboembolism remains a major cause of mortality in patients with NSCLC. We performed a retrospective cohort study to evaluate thromboembolic outcomes in patients on immunotherapy for NSCLC. Methods: We reviewed the records of all patients diagnosed with stage IV NSCLC between December 2016 and December 2019 and treated with chemotherapy, CPIs, or both in one of the largest integrated academic health systems in Western Pennsylvania. Khorana scores (to predict the risk of future VTE) were calculated for each patient based on available data at the time of diagnosis. Logistic regression analyses were done to evaluate clinical predictors of VTE. Survival outcomes were analyzed using Kaplan-Meier estimates and a log rank test was used to compare survival estimates. Data was analyzed using SPSS v26 (IBM Corp). Results: A total of 110 patients with stage IV NSCLC were identified, 87.1% had ECOG ≤2, 67.0% had adenocarcinoma and 25.7% had squamous cell carcinoma, and 39.1% had PD-L1 staining ≥50%. Immunotherapy related adverse events (IrAE) of any grade were found in 28.2%. Overall, 25.5% received chemotherapy only, 27.7% received CPIs alone, and 45.5% received chemo + CPIs. A Khorana score of ≥2 was found in 43.6% of patients. Prophylactic anticoagulation was used in 0.9% of patients. VTE was detected in 18.3% and ATE in 10.0% of the cohort; therapeutic anticoagulation was given in 14.7% of patients. Median overall survival was 25.5 months (95% CI 18.7-32.3) in patients without VTE versus 13.7 months (95% CI 3.1-24.3) in patients with a VTE diagnosis (HR 1.96, 95% CI 1.11-3.45; p = 0.02). Khorana score of ≥2 was not a significant predictor of VTE in this cohort (univariate OR 1.34, p = 0.53, multivariate OR 1.13, p = 0.81), but was associated with worse survival (HR 2.38, 95% CI 1.48-3.83, p < 0.001). Conclusions: In this retrospective cohort, VTE was associated with decreased overall survival. While no significant association between elevated Khorana score and VTE was identified, elevated Khorana score at the time of diagnosis was an independent predictor of survival in patients with NSCLC. Of note, there was a low rate of prophylactic anticoagulation in this cohort.