Sebastian Michels1, Bartomeu Massutí2, Hans-Ulrich Schildhaus3, Jeremy Franklin4, Martin Sebastian5, Enriqueta Felip6, Christian Grohé7, Delvys Rodriguez-Abreu8, Diana S Y Abdulla1, Helge Bischoff9, Christian Brandts5, Enric Carcereny10, Jesús Corral11, Anne-Marie C Dingemans12, Eva Pereira13, Jana Fassunke14, Rieke N Fischer1, Masyar Gardizi1, Lukas Heukamp15, Amelia Insa16, Anna Kron1, Roopika Menon17, Thorsten Persigehl18, Martin Reck19, Richard Riedel1, Sacha I Rothschild20, Andreas H Scheel14, Matthias Scheffler1, Petra Schmalz21, Egbert F Smit22, Meike Limburg1, Mariano Provencio23, Niki Karachaliou24, Sabine Merkelbach-Bruse14, Martin Hellmich4, Lucia Nogova1, Reinhard Büttner14, Rafael Rosell25, Jürgen Wolf26. 1. Lung Cancer Group Cologne, Department I for Internal Medicine and Center for Integrated Oncology Cologne/Bonn, University Hospital Cologne, Cologne, Germany. 2. Department of Oncology, Alicante University Hospital-ISABIAL, Alicante, Spain. 3. Institute of Pathology, University Hospital Goettingen, Göttingen, Germany and Targos Molecular Pathology, Kassel, Germany. 4. Institute of Medical Statistics and Computational Biology, University Hospital Cologne, Cologne, Germany. 5. Department of Hematology and Oncology, University Hospital of Frankfurt, Frankfurt am Main, Germany. 6. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 7. Department of Pneumology, Protestant Lung Hospital Berlin, Berlin, Germany. 8. Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. 9. Thoraxonkologie, Thoraxklinik, Heidelberg, Germany. 10. Servei d'Oncologia Mèdica, Institut Català d'Oncologia Badalona-Hospital Germans Trias i Pujol, Carretera de Canyet, Badalona, Spain. 11. Department of Medical Oncology, Clínica Universidad de Navarra, Madrid, Spain; prior affiliation during the trial: Hospital Universitario Virgen del Rocío, Sevilla, Spain. 12. Department for Oncology, Maastricht University Medical Center, Maastricht, Netherlands. 13. Spanish Lung Cancer Group, Barcelona, Spain. 14. Lung Cancer Group Cologne, Institute of Pathology and Center for Integrated Oncology Cologne/Bonn, University Hospital Cologne, Cologne, Germany. 15. Institute of Hematopatholgy Hamburg, Hamburg, Germany, and Lung Cancer Network NOWEL, Oldenburg, Germany. 16. Hospital Clínico Universitario de Valencia, València, Spain. 17. NEO New Oncology GmbH, Cologne, Germany. 18. Department of Radiology, University Hospital Cologne, Cologne, Germany. 19. Department for Thoracic Oncology, Airway Research Center North (ARCN), German Center for Lung Research, LungenClinic Grosshansdorf, Großhansdorf, Germany. 20. University Hospital Basel, Department Internal Medicine, Medical Oncology, Basel, Switzerland. 21. Clinical Trials Centre Cologne (CTCC) Medical Faculty, University of Cologne, Cologne, Germany. 22. Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands. 23. Department of Medical Oncology, Hospital Universitario Puerta de Hierro de Majadahonda, Majadahonda, Spain. 24. Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain; Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, Barcelona, Spain. 25. Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain; Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, Barcelona, Spain; Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain. 26. Lung Cancer Group Cologne, Department I for Internal Medicine and Center for Integrated Oncology Cologne/Bonn, University Hospital Cologne, Cologne, Germany. Electronic address: juergen.wolf@uk-koeln.de.
Abstract
INTRODUCTION: ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). PATIENTS AND METHODS: The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. RESULTS: Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). CONCLUSIONS: Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients.
INTRODUCTION:ROS1 rearrangements are found in 1% of lung cancerpatients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). PATIENTS AND METHODS: The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. RESULTS: Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). CONCLUSIONS:Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients.
Authors: Haiyan Xu; Quan Zhang; Li Liang; Junling Li; Zhefeng Liu; Weihua Li; Lu Yang; Guangjian Yang; Fei Xu; Jianming Ying; Shucai Zhang; Yan Wang Journal: Cancer Med Date: 2020-03-13 Impact factor: 4.452
Authors: Jessica J Lin; Noura J Choudhury; Satoshi Yoda; Aaron N Hata; Alexander Drilon; Justin F Gainor; Viola W Zhu; Ted W Johnson; Ramin Sakhtemani; Ibiayi Dagogo-Jack; Subba R Digumarthy; Charlotte Lee; Andrew Do; Jennifer Peterson; Kylie Prutisto-Chang; Wafa Malik; Harper G Hubbeling; Adam Langenbucher; Adam J Schoenfeld; Christina J Falcon; Jennifer S Temel; Lecia V Sequist; Beow Y Yeap; Jochen K Lennerz; Alice T Shaw; Michael S Lawrence; Sai-Hong Ignatius Ou Journal: Clin Cancer Res Date: 2021-03-08 Impact factor: 12.531