Marliese Alexander1, Nick Pavlakis2, Thomas John3, Rachel O'Connell4, Steven Kao5, Brett G M Hughes6, Adrian Lee2, Sarah A Hayes7, Viive M Howell7, Stephen J Clarke2, Michael Millward8, Kate Burbury9, Benjamin Solomon10, Malinda Itchins2. 1. Department of Pharmacy, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia. Electronic address: marliese.alexander@petermac.org. 2. Bill Walsh Translational Research Laboratory, Kolling Institute Medical Institute of Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Northern Clinical School, University of Sydney, St Leonards, New South Wales, Australia; Northern Cancer Institute, St Leonards, New South Wales, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia. 3. Medical Oncology Unit, Olivia Newton John Cancer and Wellness Centre, Austin Health, Melbourne, Australia; Olivia Newton-John Cancer Research Institute, Melbourne, Victoria, Australia; Department of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia. 4. NHMRC Clinical Trial Centre, University of Sydney, Camperdown, New South Wales, Australia. 5. Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. 6. Department of Medical Oncology, The Prince Charles Hospital, Chermside West, Queensland, Australia; School of Medicine, University of Queensland, Brisbane, Queensland, Australia. 7. Bill Walsh Translational Research Laboratory, Kolling Institute Medical Institute of Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Northern Clinical School, University of Sydney, St Leonards, New South Wales, Australia. 8. School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. 9. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia; Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 10. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Abstract
OBJECTIVES: This study aimed to describe the longitudinal thromboembolism (TE) risk relative to the natural history of disease and clinical course of ROS1 rearranged non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Cases of ROS1-rearranged NSCLC from six Australian hospitals were pooled and evaluated for incidence, timing, predictors and outcomes of venous or arterial TE, as well as objective response rate (ORR) to active therapy and overall survival (OS). RESULTS: Of 42 patients recruited, 20 (48%) experienced TE; one (2%) arterial, 13 (31%) a pulmonary emboli (PE), and 12 (29%) a deep vein thrombosis. Among those with TE, six (30%) experienced multiple events, three as concurrent and three as recurrent diagnoses. The cumulative incidence of TE over time, adjusted for death as a competing risk factor, approached 50%. TE occurred prior to, during and post the peri-diagnostic period and occurred irrespective of treatment strategy. A thrombophilia was identified in n = 3/10 (30%) cases screened: in two factor V Leiden and in one anti-thrombin III (ATIII) deficiency. Median OS was 21.3 months in those with TE vs. 28.8 months in those without; hazard ratio 1.16 (95%CI 0.43-3.15). Respective ORR to first-line therapy with TE was 50% vs. 44% without TE in the chemotherapy arm and 67% vs. 50% in the targeted therapy arm. CONCLUSION: In the rare cancer subtype, ROS1, these real-world data demonstrate sustained TE risk beyond the diagnostic period irrespective of therapeutic strategy. High incidence of PE, concurrent TE, and recurrent TE warrant validation in larger cohorts. Consideration of primary thromboprophylaxis in ROS1 populations is recommended.
OBJECTIVES: This study aimed to describe the longitudinal thromboembolism (TE) risk relative to the natural history of disease and clinical course of ROS1 rearranged non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Cases of ROS1-rearranged NSCLC from six Australian hospitals were pooled and evaluated for incidence, timing, predictors and outcomes of venous or arterial TE, as well as objective response rate (ORR) to active therapy and overall survival (OS). RESULTS: Of 42 patients recruited, 20 (48%) experienced TE; one (2%) arterial, 13 (31%) a pulmonary emboli (PE), and 12 (29%) a deep vein thrombosis. Among those with TE, six (30%) experienced multiple events, three as concurrent and three as recurrent diagnoses. The cumulative incidence of TE over time, adjusted for death as a competing risk factor, approached 50%. TE occurred prior to, during and post the peri-diagnostic period and occurred irrespective of treatment strategy. A thrombophilia was identified in n = 3/10 (30%) cases screened: in two factor V Leiden and in one anti-thrombin III (ATIII) deficiency. Median OS was 21.3 months in those with TE vs. 28.8 months in those without; hazard ratio 1.16 (95%CI 0.43-3.15). Respective ORR to first-line therapy with TE was 50% vs. 44% without TE in the chemotherapy arm and 67% vs. 50% in the targeted therapy arm. CONCLUSION: In the rare cancer subtype, ROS1, these real-world data demonstrate sustained TE risk beyond the diagnostic period irrespective of therapeutic strategy. High incidence of PE, concurrent TE, and recurrent TE warrant validation in larger cohorts. Consideration of primary thromboprophylaxis in ROS1 populations is recommended.
Authors: Alok A Khorana; Nigel Mackman; Anna Falanga; Ingrid Pabinger; Simon Noble; Walter Ageno; Florian Moik; Agnes Y Y Lee Journal: Nat Rev Dis Primers Date: 2022-02-17 Impact factor: 65.038