Risk of thromboembolism in non-small-cell lung cancers patients with different oncogenic drivers, including ROS1, ALK, and EGFR mutations

Background: Anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1 (ROS1)-positive (ROS1+) lung cancers have been reported to be associated with an elevated risk of thromboembolic events. This study aimed to assess the long-term risk of developing thromboembolism (TE) in ROS1+ lung cancer and to compare it with other oncogenic drivers in the Asian population. Materials and methods: We retrospectively enrolled a cohort of ROS1+ lung adenocarcinoma in a medical center in Taiwan and a comparison cohort of ALK+ and epidermal growth factor receptor-positive (EGFR+) lung cancers. Venous and arterial TEs were identified throughout the cancer course, and the incidence rate was calculated. Results: We enrolled 44 ROS1+, 98 ALK+, and 168 EGFR+ non-small-cell lung cancer (NSCLC) patients. A total of 11 (25%), 36 (36.7%), and 38 (22.6%) patients in the ROS1, ALK, and EGFR cohorts, respectively, were diagnosed with thromboembolic events throughout the follow-up course of the disease (P = 0.042). The incidence rates were 99.0, 91.9, and 82.5 events per 1000 person-years for the ROS1, ALK, and EGFR cohorts, respectively. The majority of thrombosis events in the ROS1 (91.6%) and ALK (85.4%) cohorts were venous. On the contrary, 43.2% of thromboembolic events were arterial in the EGFR cohort. A higher proportion of thromboembolic events were noted during cancer diagnosis in the ROS1 cohort (36.3%) than in the ALK (16.7%) and EGFR (10.5%) cohorts. The stage was the only clinical variable associated with thromboembolic risk. There was a significant difference in survival between patients with and without TE in the EGFR cohort, but not in the ALK and ROS1 cohorts. Conclusions: Although ROS1+ and ALK+ NSCLCs had a higher cumulative incidence of TE than EGFR+ NSCLC, the person-year incidence rates were similar among the three groups. EGFR-mutated NSCLC had more arterial events. Nevertheless, ALK+ lung cancer had higher venous events than EGFR-mutated lung cancer.