Original Study ROS1-rearranged Nonesmall-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS) Rita Chiari, 1 Biagio Ricciuti, 1 Lorenza Landi, 2 Anna M. Morelli, 3 Angelo Delmonte, 4 Gianluca Spitaleri, 5 Diego L. Cortinovis, 6 Giuseppe Lamberti, 7 Francesco Facchinetti, 8 Sara Pilotto, 9 Claudio Verusio, 10 Antonio Chella, 11 Laura Bonanno, 12 Domenico Galetta, 13 Federico Cappuzzo 2 Abstract The incidence of venous thromboembolism (VTE) in patients with oncogene-addicted nonesmall-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. Background: Patients with cancer are at increased risk for venous thromboembolism (VTE), and 8% to 15% of pa- tients with advanced nonesmall-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 effi- cacy, 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 R.C. and B.R. contributed equally to this article as first authors. 1 Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy 2 AUSL Romagna, Dipartimento di Oncologia ed Ematologia, Ravenna, Italy 3 Dipartimento di Oncologia, Università di Torino, Torino, Italy 4 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy 5 Thoracic Oncology Division, Istituto Europeo di Oncologia IRCSS, Milano, Italy 6 SC Oncologia Medica, SS Lung Unit Asst Ospedale San Gerardo, Monza, Italy 7 Department of Specialized, Experimental, and Diagnostic Medicine, Bologna, Italy 8 Dipartimento di Medicina e Chirurgia, Università degli Studi di Parma e Oncologia Medica, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy 9 Department of Medical Oncology, University Hospital of Verona, Verona, Italy 10 Ospedale di Saronno, Saronno, Italy 11 Azienda Ospedaliero Universitaria Pisana, Pisa, Italy 12 Istituto Oncologico Veneto, Padova, Italy 13 Oncologia Medica Toracica, IRCCS Oncologico Giovanni Paolo II, Bari, Italy Submitted: Apr 4, 2019; Revised: May 9, 2019; Accepted: Jun 7, 2019; Epub: Jun 18, 2019 Address for correspondence: Biagio Ricciuti, MD, Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy E-mail contact: biagio.ricciuti@gmail.com 1525-7304/$ - see frontmatter ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.cllc.2019.06.012 Clinical Lung Cancer January 2020 - 15