Incidence, risk factors and clinical outcome of venous thromboembolism in non-small cell lung cancer patients receiving immune checkpoint inhibition

Background: Besides the cancer itself, venous thromboembolism (VTE) is the leading cause of death in cancer patients receiving outpatient chemotherapy (CT). Data on VTE development and impact on treatment course and outcome in real-life NSCLC patients receiving immune check-point inhibitors (ICI) is currently sparse. More knowledge within this area is warranted due to the emerging use of ICI in clinical practice. Objectives: To quantify risk of VTE and recurrent VTE in NSCLC patients receiving ICI. Explore the clinical impact of VTE on ICI course and survival and explore potential risk factors for VTE. Patients/methods: Patients with advanced/metastatic NSCLC treated with an immune checkpoint inhibitor (ICI) at the University Hospital of Odense, Denmark during 2015–2018 were identified and data gathered retrospectively from electronic medical records (n = 118). All patients had finished ICI at the time of data-cut off. Baseline Khorana Score (KRS) was calculated within one week prior to ICI initiation. Based on follow-up data cumulative incidence of VTE and its impact on outcome and survival was performed using Kaplan Meier and cox-regression hazard estimation. Results: Risk of VTE was 8% during ICI and 15% at any time point after ICI initiation. Cumulative incidence rates of VTE at 1, 3, 6 and 18 months after first ICI was 1.7%, 5.2%, 6.9% and 13.8% respectively. Median time to VTE during ICI was 2.3 months [IQR 0.6–5.4]. Having VTE during ICI lead to discontinuation of ICI in 78% of cases, most due to fatal PE. History of VTE before onset of ICI was a significant risk factor for recurrent VTE during ICI (24% within this subgroup) despite use of anticoagulant therapy. Conclusions: The incidence and impact of VTE during ICI for real-life NSCLC patients is not negligible with almost 10% developing VTE leading to termination of further ICI in the majority of cases - many due to fatal PE. The risk of recurrent anticoagulant resistant VTE in patients with known VTE during ICI is also considerable, which calls for better management and prevention of VTE including development of treatment specific VTE risk assessment models

Effect and Tolerability of Immunotherapy in Patients with NSCLC with or without Brain Metastasis

Sparse data exist on immune checkpoint inhibition (ICI) in NSCLC patients with brain metastasis (BM), especially for those with no local therapy (LT) (whole brain radiation therapy (WBRT), stereotactic RT (SRT) or neurosurgery) preceding ICI. Our aims were to investigate the prevalence of BM, rate of intracranial response (ICR), and survival and quality of life (QoL) in real-life patients with advanced NSCLC undergoing palliative ICI. This was a prospective non-randomized study (NCT03870464) with magnetic resonance imaging of the brain (MR-C) performed at baseline resulting in a clinical decision to administer LT or not. ICR evaluation (MR-C) at week 8–9 (mRECIST criteria) for group A (LT) and group B (untreated) was assessed. Change in QoL was assessed using EQ-5D-5L. Of 159 included patients, 45 (28%) had baseline BM. Median follow-up was 23.2 months (IQR 16.4–30.2). Of patients in group A (21) and B (16), 16/37 (43%) had symptomatic BM. ICR was 8/21, 38% (complete or partial response) for group A versus 8/16, 50% for group B. No statistical difference in median overall survival of patients with BM (group A: 12.3 (5.2-NR), group B: 20.5 months (4.9-NR)) and without (22.4 months (95% 16.2–26.3)) was obtained. Baseline QoL was comparable regardless of BM, but an improved QoL (at week 9) was found in those without BM. Patients with NSCLC and BM receiving ICI had long-term survival comparable to those without BM