Thromboembolism in ALK+ and ROS1+ NSCLC patients: A systematic review and meta-analysis

Abstract

Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC). Materials and Methods: Odds ratios (OR) and hazard ratios (HR) of TE were calculated from meta-analysis and time-to-event analysis respectively for either ALK+ or ROS1+ NSCLC patients. Results: We identified eight studies (766 ALK+, 143 ROS1+, 2314 non-ALK+ and non-ROS1+ NSCLC patients) for the meta-analysis. For ALK+ NSCLC, the pooled OR was 2.00 (95% CI: 1.60-2.50) for total TE (TTE) by random-effects model, 2.10 (95% CI: 1.70-2.60) for venous thromboembolism (VTE), and 1.24 (95% CI: 0.80-1.91) for arterial thromboembolism (ATE). For ROS1+ NSCLC, the pooled OR was 3.08 (95% CI: 1.95-4.86) for TTE, and 3.15 (95% CI: 1.83-5.43) for VTE. Six studies (739 ALK+, 137 ROS1+, 561 EGFR+, 714 "wildtype" NSCLC patients) were included in the time-to-event analysis. The TTE incidence rate was 17.4 (95% CI: 15.3-19.5) per 100 pateint-years for ALK+ NSCLC, and 32.1 (95% CI: 24.6-39.6) per 100 patient-years for ROS1+ NSCLC with a 50 % cumulative incidence rate at year 3 of diagnosis. HR for TTE was 2.35 (95% CI: 1.90-2.92, p < 0.001) and 3.23 (95% CI: 2.40-4.34, p < 0.001) for ALK+ and ROS1+ NSCLC, respectively. Comparing ROS1+ NSCLC to ALK+ NSCLC, HR for TTE was 1.37 (95% CI: 1.05-1.79, p = 0.020). Conclusions: ALK+ and ROS1+ NSCLC patients had an increased risk of TE. ROS1+ NSCLC had further increased risk of TE over ALK+ NSCLC.

Romiplostim for chemotherapy‐induced thrombocytopenia: Efficacy and safety of extended use

“…Her tumor had wild‐type KRAS , but exhibited ALK‐EML4 fusion and MET amplification, both associated with a significant increase in VTE rates. 20 , 21 Her platelet count was 23 × 10 9 /L at the time of the splenic and renal infarct and 210 × 10 9 /L and 21 × 10 9 /L at the time of the two cerebral vascular events. The subject and her oncologist decided to continue romiplostim, as her cancer was responding well to ongoing chemotherapy, and without romiplostim, thrombocytopenia precluded her from receiving optimal anticoagulation.…”

Multiple organ infarction caused by aortic thrombus in a lung cancer patient with the BRAF mutation

“…Ortega et al reported that 28.6% (6/21) of patients with colorectal cancer harboring BRAF mutations developed thrombosis, compared with 21.9% (23/105) of those without BRAF mutation [ 13 ] . Although the underlying mechanisms are unknown, the activation of oncogenes induces the expression of genes associated with tissue factors that control hemostasis [ 8 , 12 , 13 , 17 , 18 ].…”

“…Patients with lung cancer in particular had the highest rates of arterial thrombosis (8.3%). Furthermore, oncogenic driver genes are reported to be associated with thrombosis [ 8 ]. The V-Raf murine sarcoma viral oncogene homolog B1 ( BRAF ) mutation acts as an oncogenic driver gene in solid cancers including lung cancer [ [9] , [10] , [11] ].…”

Targeting ALK Rearrangements in NSCLC: Current State of the Art

“…ALK+ NSCLC patients tend to be younger, with no smoking history, and have adenocarcinoma as the most common histological subtype ( 14 ). A recent meta-analysis confirmed that there is an increased incidence of thromboembolism in ALK+ NSCLC patients as compared to non-ALK+ patients ( 15 ). Real-world data also suggested an increased risk of venous thromboembolism in ALK-rearranged NSCLC patients ( 16 , 17 ).…”