P90.02 BRAF Mutation And Peridiagnosis Thromboembolic Events In Advanced NSCLC Patients

Abstract

Metastatic lung cancer is associated with an increased risk of thromboembolic events (TEE). Certain molecular subtypes of lung cancer, as patients with tumors harboring ALK or ROS1 gene rearrangements, have been recently associated with higher risk of TEE, in the range of 20-30%. Whether BRAF mutant lung cancer is associated with higher risk of TEE is unknown. We aimed to describe the incidence, characteristics, and time of onset of TEE in advanced BRAF mutant non-small-cell lung cancer (NSCLC) patients. We performed a retrospective search of BRAF mutant advanced NSCLC patients (stage IIIB or greater) diagnosed in our institution between October 2016 and February 2020. BRAF status was assessed by NGS in tissue/plasma or both as part of molecular pre-screening for clinical trials (Oncomine Focus Assay®; FoundationOne®; Guardant360®). Clinicopathologic and molecular data were extracted from electronic medical records. BRAF mutations were annotated and divided into Class I (V600) and Class II/III/VUS (non-V600) using OncoKB database. Venous TEE (deep venous thrombosis [DVT], superficial venous thrombosis [SVT] or pulmonary embolism [PE]) and arterial TEE (myocardial infarction [MI], cerebrovascular accident [CVA], peripheral arterial disease [PAD] or mesenteric ischemia [MIS]), number of events and dates were annotated. BRAF mutation was identified in 11/192 patients (incidence 5.7%): BRAF V600E in 2 cases (1%), and non-V600 in 9 cases (4.7%). Adenocarcinoma was the histology for all the cases. The incidence rate of TEE was 36.4% (4/11 patients). A total of 9 TEE were documented among 4 patients, as 3 of them developed several events, both arterial and venous. The TEE were DVT (n=2), SVT (n=1), PE (n=2), CVA (n=3), MIS (n=1). TEE was the form of disease presentation in 3/4 cases (acute stroke in 2 cases). TEE were found in 1 patient with V600E mutation and in 3 with non-V600. TEE were found more frequently in patients with PS ≥1, low albumin and Khorana score ≥2. Type of treatment was not related to TEE: 1 patient BRAF V600E mutated was treated with dabrafenib + trametinib without TEE, 4 patients were treated with immune-checkpoint inhibitors (1 with TEE) and 2 cases of TEE were detected before the initiation of treatment. Median overall survival was shorter in patients with TEE vs. without-TEE: 2.3 months vs 29 months (p=0.047). BRAF mutant lung cancer could be associated with a higher risk of TEE, both arterial and venous, and worse survival. If these results are confirmed in larger cohorts, prophylactic anticoagulation may be recommended in these patients.