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Crizotinib in Patients with Lung Cancer and Ros1 Fusion: Results from the European Cohort Euros1.
Annals of Oncology 25 (Supplement 4): iv426–iv470, 2014 doi:10.1093/annonc/mdu349.77
NSCLC, metastatic 1298P
CRIZOTINIB IN PATIENTS WITH LUNG CANCER AND ROS1 FUSION: RESULTS FROM THE EUROPEAN COHORT EUROS1.
abstracts
Aim: ROS1 chromosomal rearrangement (ROS1+) is an oncogenic driver in approximately 1% of non-small cell lung cancers (NSCLC). Due to the structural analogy of ROS1 and ALK, crizotinib is a potent inhibitor of both kinases. A phase I
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv457/2242017 by guest on 26 October 2019
J. Mazières1, G. Zalcman2, L. Crinò3, P. Biondani4, T. Filleron5, A.C. Dingemans6, H. Lena7, I. Monnet8, S.I. Rothschild 9, F. Cappuzzo10, L. Thiberville11, F. Barlesi12, R. Dziadziuszko13, E.F. Smit14, J. Wolf15, C. Spirig16, N. Pecuchet17, J. Diebold18, J. Milia1, O. Gautschi19 1 Thoracic Oncology, Larrey, Toulouse University Hospital, Toulouse, FRANCE 2 Service de Pneumologie, C.H.U. de Caen, Caen, FRANCE 3 Department of Medical Oncology, Ospedale Santa Maria della Misericordia, Perugia, ITALY 4 Cancer Campus, Grand Paris, Institut Gustave Roussy, Villejuif, FRANCE 5 Cellule Biostatistique-bec, Institut Universitaire du Cancer, Toulouse, FRANCE 6 Pulmonology, Maastricht University Medical Center (MUMC), Maastricht, NETHERLANDS 7 Pneumologie, Hopital Pontchaillou, Rennes, FRANCE 8 Pulmonology, Centre Hospitalier intercommunal de Creteil, Creteil, FRANCE 9 Medical Oncology, Universitätsspital Basel, Basel, SWITZERLAND 10 U.O. Oncologia Medica, Istituto Toscano Tumori-Ospedale Civile-Livorno-Italy, Pisa, ITALY 11 Pneumologie, Hôpital Charles Nicolle, CHU Rouen, Rouen, FRANCE 12 Multidisciplinary Oncology & Therapeutic Innovatio, Hopital Nord, Marseille, FRANCE 13 Dept. of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, POLAND 14 Dept. of Pulmonary Diseases, Vrije University Medical Centre (VUMC), Amsterdam, NETHERLANDS 15 Internal Medicine Clinic, University of Cologne, Cologne, GERMANY 16 Pulmonology, Luzerner Kantonsspital, Lucerne, SWITZERLAND 17 Dept. Medical Oncology, Hopital European George Pompidou, Paris, FRANCE 18 Pulmonology, Pathologisches Institut, Lucerne, SWITZERLAND 19 Klinik für Onkologie, Luzerner Kantonsspital, Lucerne, SWITZERLAND
trial [Ou et al., WCLC 2013] showed promising activity of crizotinib in ROS1+ NSCLC. Methods: In the absence of a dedicated clinical trial in Europe, we conducted a retrospective study in European centers testing patients for ROS1. Eligible patients had advanced NSCLC, ROS1 fusion diagnosed by FISH and therapy with crizotinib at the dose of 250 mg BID through national access program or an individual off-label use basis. Treatment response was assessed according to RECIST criteria. Informed consent was obtained according to local regulations. Data were analyzed centrally. Results: We identified 32 ROS1+ NSCLC patients treated with crizotinib in 17 centers from 6 countries in 2013 and 2014. Our population was characterized by a median age of 55 years, a majority of female (63%) and of never smokers (69%). All the patients had adenocarcinoma (including 4 with lepidic features) and stage IV disease. All but one were pretreated with chemotherapy. ROS1 rearrangement was the exclusive driver except for 2 tumors with concomitant KRAS mutation. Thirty-one patients were evaluable for response. We observed 5 progressive diseases, 3 stable diseases and 23 objective responses including 5 complete responses (Overall Response Rate 74%, Disease Control Rate 84%). Median progression free survival (PFS) was not reached and PFS at 12 months was 69.9 %. Crizotinib primary resistance was associated with concomitant KRAS mutation in 2 patients and with isolated brain progression in 1 patient. Crizotinib was generally well tolerated and no unexpected adverse effects were observed. Most of the patients (n = 27, 84%) also received pemetrexed (before or after crizotinib) with a 7.6 months median PFS. Conclusions: Crizotinib is highly active in ROS1+ NSCLC underlining the interest of integrating ROS1 in biomarkers screening of advanced adenocarcinoma. Further patients should be treated in ongoing clinical trials to test the long-term activity of crizotinib and new potent ROS1 inhibitors. Disclosure: L. Crinò: I have received honoraria from Pfitzer, as speaker or as participant at advisory board; A.C. Dingemans: I have been advisory Board for Pfizer (compensated); H. Lena: Participation to the Pfizer’s board meeting; S.I. Rothschild: I received honoraria for the participation in advisory boards from Pfizer and for presentations at scientific symposiums sponsored by Pfizer; F. Cappuzzo: I declare that I provided lectures, consultancy and Ad Boards for Pfizer, Roche Astrazeneca; L. Thiberville: I have received 750 Euros Honorarium from Pfizer for the participation to a board of expert (2012); R. Dziadziuszko: Advisory board and speaker’s bureau for Pfizer (compensated; J. Wolf: I received honoraria for advisory boards and talks on symposia as well as research support from Pfizer; N. Pecuchet: I have received honorarium from Novartis, Amgen, GSK and Roche; J. Diebold: I am member of advisory boards for Pfizer, Astra-Zeneca, Roche. All other authors have declared no conflicts of interest.
NSCLC, metastatic 1298P
CRIZOTINIB IN PATIENTS WITH LUNG CANCER AND ROS1 FUSION: RESULTS FROM THE EUROPEAN COHORT EUROS1.
abstracts
Aim: ROS1 chromosomal rearrangement (ROS1+) is an oncogenic driver in approximately 1% of non-small cell lung cancers (NSCLC). Due to the structural analogy of ROS1 and ALK, crizotinib is a potent inhibitor of both kinases. A phase I
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv457/2242017 by guest on 26 October 2019
J. Mazières1, G. Zalcman2, L. Crinò3, P. Biondani4, T. Filleron5, A.C. Dingemans6, H. Lena7, I. Monnet8, S.I. Rothschild 9, F. Cappuzzo10, L. Thiberville11, F. Barlesi12, R. Dziadziuszko13, E.F. Smit14, J. Wolf15, C. Spirig16, N. Pecuchet17, J. Diebold18, J. Milia1, O. Gautschi19 1 Thoracic Oncology, Larrey, Toulouse University Hospital, Toulouse, FRANCE 2 Service de Pneumologie, C.H.U. de Caen, Caen, FRANCE 3 Department of Medical Oncology, Ospedale Santa Maria della Misericordia, Perugia, ITALY 4 Cancer Campus, Grand Paris, Institut Gustave Roussy, Villejuif, FRANCE 5 Cellule Biostatistique-bec, Institut Universitaire du Cancer, Toulouse, FRANCE 6 Pulmonology, Maastricht University Medical Center (MUMC), Maastricht, NETHERLANDS 7 Pneumologie, Hopital Pontchaillou, Rennes, FRANCE 8 Pulmonology, Centre Hospitalier intercommunal de Creteil, Creteil, FRANCE 9 Medical Oncology, Universitätsspital Basel, Basel, SWITZERLAND 10 U.O. Oncologia Medica, Istituto Toscano Tumori-Ospedale Civile-Livorno-Italy, Pisa, ITALY 11 Pneumologie, Hôpital Charles Nicolle, CHU Rouen, Rouen, FRANCE 12 Multidisciplinary Oncology & Therapeutic Innovatio, Hopital Nord, Marseille, FRANCE 13 Dept. of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, POLAND 14 Dept. of Pulmonary Diseases, Vrije University Medical Centre (VUMC), Amsterdam, NETHERLANDS 15 Internal Medicine Clinic, University of Cologne, Cologne, GERMANY 16 Pulmonology, Luzerner Kantonsspital, Lucerne, SWITZERLAND 17 Dept. Medical Oncology, Hopital European George Pompidou, Paris, FRANCE 18 Pulmonology, Pathologisches Institut, Lucerne, SWITZERLAND 19 Klinik für Onkologie, Luzerner Kantonsspital, Lucerne, SWITZERLAND
trial [Ou et al., WCLC 2013] showed promising activity of crizotinib in ROS1+ NSCLC. Methods: In the absence of a dedicated clinical trial in Europe, we conducted a retrospective study in European centers testing patients for ROS1. Eligible patients had advanced NSCLC, ROS1 fusion diagnosed by FISH and therapy with crizotinib at the dose of 250 mg BID through national access program or an individual off-label use basis. Treatment response was assessed according to RECIST criteria. Informed consent was obtained according to local regulations. Data were analyzed centrally. Results: We identified 32 ROS1+ NSCLC patients treated with crizotinib in 17 centers from 6 countries in 2013 and 2014. Our population was characterized by a median age of 55 years, a majority of female (63%) and of never smokers (69%). All the patients had adenocarcinoma (including 4 with lepidic features) and stage IV disease. All but one were pretreated with chemotherapy. ROS1 rearrangement was the exclusive driver except for 2 tumors with concomitant KRAS mutation. Thirty-one patients were evaluable for response. We observed 5 progressive diseases, 3 stable diseases and 23 objective responses including 5 complete responses (Overall Response Rate 74%, Disease Control Rate 84%). Median progression free survival (PFS) was not reached and PFS at 12 months was 69.9 %. Crizotinib primary resistance was associated with concomitant KRAS mutation in 2 patients and with isolated brain progression in 1 patient. Crizotinib was generally well tolerated and no unexpected adverse effects were observed. Most of the patients (n = 27, 84%) also received pemetrexed (before or after crizotinib) with a 7.6 months median PFS. Conclusions: Crizotinib is highly active in ROS1+ NSCLC underlining the interest of integrating ROS1 in biomarkers screening of advanced adenocarcinoma. Further patients should be treated in ongoing clinical trials to test the long-term activity of crizotinib and new potent ROS1 inhibitors. Disclosure: L. Crinò: I have received honoraria from Pfitzer, as speaker or as participant at advisory board; A.C. Dingemans: I have been advisory Board for Pfizer (compensated); H. Lena: Participation to the Pfizer’s board meeting; S.I. Rothschild: I received honoraria for the participation in advisory boards from Pfizer and for presentations at scientific symposiums sponsored by Pfizer; F. Cappuzzo: I declare that I provided lectures, consultancy and Ad Boards for Pfizer, Roche Astrazeneca; L. Thiberville: I have received 750 Euros Honorarium from Pfizer for the participation to a board of expert (2012); R. Dziadziuszko: Advisory board and speaker’s bureau for Pfizer (compensated; J. Wolf: I received honoraria for advisory boards and talks on symposia as well as research support from Pfizer; N. Pecuchet: I have received honorarium from Novartis, Amgen, GSK and Roche; J. Diebold: I am member of advisory boards for Pfizer, Astra-Zeneca, Roche. All other authors have declared no conflicts of interest.