ROS1-rearranged Non–small-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS): Clinical Lung Cancer

R. Chiari, B. Ricciuti, L. Landi, A.M. Morelli, A. Delmonte, G. Spitaleri, D.L. Cortinovis, G. Lamberti, F. Facchinetti, S. Pilotto, C. Verusio, A. Chella, L. Bonanno, D. Galetta, F. Cappuzzo

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Patients with cancer are at increased risk for venous thromboembolism (VTE), and 8% to 15% of patients with advanced non–small-cell lung cancer (NSCLC) experience a VTE event during the course of their disease. The incidence of VTE in molecularly defined NSCLC subgroups is still unclear. In this study, we investigated the incidence and the clinical correlates of VTE in patients with ROS1-rearranged NSCLC enrolled in the METROS trial (NCT02499614). Patients and Methods: The METROS trial is a prospective phase II study designed to assess efficacy, safety, and tolerability of crizotinib in patients with pre-treated metastatic NSCLC ROS1 rearrangement (cohort A) or with MET amplification or MET exon 14 mutation (cohort B). Patients with ROS1-rearranged NSCLC enrolled within cohort A and the expansion cohort of the trial were included in the primary analysis. Results: Among 48 patients with ROS1-rearranged NSCLC enrolled in the METROS study, 20 (41.6%) of 48 had at least 1 VTE event. Among them, 7 (35%) of 20 patients had ≥ 2 VTE events. VTE events consisted of pulmonary embolism (46.4%), deep vein thrombosis (39.2%), renal vein thrombosis (7.1%), internal jugular thrombosis (3.5%), and peripheral inserted central catheter-related thrombosis (3.5%). VTE events occurred at disease progression in 35.7% of cases, at diagnosis in 32.1% of cases, and during chemotherapy or crizotinib in 17.8% and 14.2%, respectively. Conclusion: The incidence of VTE is 3- to 5-fold higher in patients harboring ROS1-rearrangment than previously observed for the general population with NSCLC. Larger studies are warranted to confirm our findings and determine whether the molecular profile of NSCLC should be incorporated into a risk-stratification tool and decision-making algorithm for VTE diagnosis and prophylaxis. © 2019 Elsevier Inc. The incidence of venous thromboembolism (VTE) in patients with oncogene-addicted non–small-cell lung cancer (NSCLC) is still in need of further investigation. In this study, we demonstrated a higher incidence of VTE in patients with advanced ROS1-rearranged NSCLC, which was 3- to 5-fold higher compared with the general population with NSCLC. Our results suggest that the molecular profile of NSCLC should be incorporated into a risk-stratification tool and decision-making algorithm for VTE diagnosis and prophylaxis. © 2019 Elsevier Inc.
Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalClin. Lung Cancer
Volume21
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • Crizotinib
  • MET
  • NSCLC
  • ROS1
  • VTE
  • crizotinib
  • pemetrexed
  • adult
  • aged
  • arterial thromboembolism
  • Article
  • cancer chemotherapy
  • cancer incidence
  • cancer staging
  • catheter thrombosis
  • clinical article
  • cohort analysis
  • controlled study
  • deep vein thrombosis
  • disease exacerbation
  • drug efficacy
  • drug safety
  • drug tolerability
  • exon
  • female
  • gene mutation
  • gene rearrangement
  • human
  • internal jugular thrombosis
  • kidney vein thrombosis
  • lung embolism
  • male
  • multicenter study
  • non small cell lung cancer
  • personal experience
  • phase 2 clinical trial
  • prospective study
  • ros1 gene
  • thrombosis prevention
  • tumor gene
  • venous thromboembolism

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