Nir Peled1, Roni Gillis2, Saadettin Kilickap3, Patrizia Froesch4, Sergei Orlov5, Elena Filippova5, Umut Demirci6, Petros Christopoulos7, Irfan Cicin8, Fatma Bugdayci Basal9, Cengiz Yilmaz10, Moiseenko Fedor11, Taner Korkmaz12, Semra Paydas13, Oliver Gautschi14, Alisan Zirtiloglu15, Yesim Eralp12, Havva Yesil Cinkir16, Ahmet Sezer17, Mustafa Erman3, Deniz Tural15, Hande Turna18, Julien Mazieres19, Elizabeth Dudnik20, Noemi Reguart21, David Ross Camidge22, Terry L Ng23, Filiz Çay Şenler24, İsmail Beypınar25, Doğan Yazılıtaş26, Ahmet Demirkazık24, Aziz Karaoğlu27, Kerem Okutur28, Hasan Şenol Coşkun29, Mehmet Ali Nahit Şendur26, Abdurrahman Isikdogan29, Devrim Cabuk30, Perran Fulden Yumuk31, Ibrahim Yıldız12, M Ali Kaplan29, Özgür Özyılkan17, İlhan Öztop27, Omer Fatih Olmez32, Kübra Aydin33, Adnan Aydıner34, Nezih Meydan35, Roxana Denisa Grinberg2, Laila C Roisman2. 1. The Legacy Heritage Oncology Center & Dr. Larry Norton Institute, Soroka Medical Center, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel. Electronic address: peled.nir@gmail.com. 2. The Legacy Heritage Oncology Center & Dr. Larry Norton Institute, Soroka Medical Center, Beer-Sheva, Israel; Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel. 3. Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey. 4. Oncology Institute of the Southern Switzerland, Bellinzona, Switzerland. 5. Pavlov First Saint Petersburg State Medical University, St Petersburg, Russia. 6. Uskudar University, Faculty of Medicine, Department of Medical Oncology, Turkey. 7. Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, and Translational Lung Research Heidelberg, Member of the German Center for Lung Research (DZL), Germany. 8. Trakya University, Faculty of Medicine, Department of Medical Oncology, Turkey. 9. University of Health Sciences, Dr. A.Y. Ankara Oncology Hospital, Department of Medical Oncology, Turkey. 10. Ege University, Faculty of Medicine, Department of Medical Oncology, İzmir, Turkey. 11. N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, 197798, Russian Federation; St. PetersburgClinical Research and Practical Center for Specialized Types of Medical Care (Oncologic), St. Petersburg, 197758, Russian Federation. 12. Acibadem MAA University Hospital, School of Medicine, Department of Medical Oncology, Maslak Hospital, İstanbul, Turkey. 13. Department of Oncology, Cukurova University Faculty of Medicine, Adana, Turkey. 14. University of Berne and Cantonal Hospital of Lucerne, Switzerland. 15. Department of Medical Oncology, Bakirkoy Sadi Konuk Training and Research Hospital, Istanbul, Turkey. 16. Gaziantep University, Faculty of Medicine, Department of Medical Oncology, Gaziantep, Turkey. 17. Adana Baskent University, Faculty of Medicine, Department of Medical Oncology, Adana, Turkey. 18. Cerrahpasa University, Faculty of Medicine Department of Medical Oncology, Istanbul, Turkey. 19. Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France. 20. Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, 49100, Israel. 21. Division of Medical Oncology, Hospital Clínic, Barcelona,Spain; Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. 22. Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, 1665 North Aurora Court, Aurora, CO, 80045, USA. 23. Ankara University Faculty of Medicine, Department of Medical Oncology, Ankara, Turkey. 24. Department of Medical Oncology, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey. 25. Yildirim Beyazit University Faculty of Medicine, Department of Medical Oncology, Ankara, Turkey. 26. Dokuz Eylul University Faculty of Medicine, Department of Medical Oncology, Izmir, Turkey. 27. Medicalpark Bahçelievler Hospital, Department of Medical Oncology, Istanbul, Turkey. 28. Akdeniz University Faculty of Medicine, Department of Medical Oncology, Antalya, Turkey. 29. Dicle University Faculty of Medicine, Department of Medical Oncology, Diyarbakir, Turkey. 30. Kocaeli University, Division of Medical Oncology, Kocaeli, Turkey. 31. Marmara University Faculty of Medicine, Department of Medical Oncology, Istanbul, Turkey. 32. Medipol University Faculty of Medicine, Department of Medical Oncology, Istanbul, Turkey. 33. Memorial Ankara Hospital, Ankara, Turkey. 34. Istanbul University Institute of Cancer, Department of Medical Oncology, Istanbul, Turkey. 35. Adnan Menderes Univesity Faculty of Medicine, Turkey.
Abstract
Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ± 1.6 months and median overall survival (mOS) was 89.1 ± 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ± 2.5 months and mOS of 90.3 ± 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ± 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ± 24 months is unprecedented for ROS1(+) NSCLC.
Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLCpatients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ± 1.6 months and median overall survival (mOS) was 89.1 ± 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ± 2.5 months and mOS of 90.3 ± 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION:Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ± 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ± 24 months is unprecedented for ROS1(+) NSCLC.
Authors: Francesco Facchinetti; Antonin Levy; Samy Ammari; Charles Naltet; Pernelle Lavaud; Mihaela Aldea; Damien Vasseur; David Planchard; Benjamin Besse Journal: Cancer Manag Res Date: 2021-03-26 Impact factor: 3.989
Authors: Sergey V Orlov; Aglaya G Iyevleva; Elena A Filippova; Alexandra M Lozhkina; Svetlana V Odintsova; Tatiana N Sokolova; Natalia V Mitiushkina; Vladislav I Tiurin; Elena V Preobrazhenskaya; Alexandr A Romanko; Alexandr S Martianov; Alexandr O Ivantsov; Svetlana N Aleksakhina; Alexandr V Togo; Evgeny N Imyanitov Journal: Transl Oncol Date: 2021-05-21 Impact factor: 4.243