Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

5840 - Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase 2 clinical trial – Updated progression-free survival, overall survival and mechanisms of resistance

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Sebastian Michels

Citation

Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260

Authors

S. Michels1, B. Massuti2, H. Schildhaus3, J. Franklin4, M. Sebastian5, E. Felip6, C. Grohe7, D.F. Rodríguez-Abreu8, H. Bischoff9, E. Carcereny Costa10, J. Corral Jaime11, A. Insa12, M. Reck13, M. Scheffler1, N. Karachaliou14, S. Merkelbach-Bruse15, L. Nogova1, R. Büttner16, R. Rosell17, J. Wolf1

Author affiliations

  • 1 Department I For Internal Medicine, University Hospital Cologne, 50937 - Köln/DE
  • 2 Department Of Medical Oncology, Hospital General Universitario de Alicante, 03010 - Alicante/ES
  • 3 Institute Of Pathology, University Hospital of Essen, 45147 - Essen/DE
  • 4 Institute Of Medical Statistics And Computational Biology, University of Cologne, 50937 - Köln/DE
  • 5 Department Of Hematology/medical Oncology, Universitätsklinikum Frankfurt(Johannes-Wolfgang Goethe Institute), 60590 - Frankfurt am Main/DE
  • 6 Medical Oncology Service (lung Cancer Unit)  , Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 7 Pneumology, Evangelische Lungenklinik ELK Berlin Chest Hospital, 13125 - Berlin/DE
  • 8 Servicio De Oncología Médica, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria/ES
  • 9 Oncology, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 10 Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 8916 - Badalona/ES
  • 11 Medical Oncology, Clínica Universitaria de Navarra, 28027 - Madrid/ES
  • 12 Medical Oncology Department, Hospital Clínico Universitario de Valencia, Valencia/ES
  • 13 Thoracic Oncology, Krankenhaus Grosshansdorf, 22927 - Grosshansdorf/DE
  • 14 Oncology, Hospital Universitari Sagrat Cor - Group Quirónsalud, 08029 - Barcelona/ES
  • 15 Institute Of Pathology, University Hospital Cologne, 50937 - Köln/DE
  • 16 Institute For Pathology, University Hospital of Cologne, 50937 - Köln/DE
  • 17 Laboratory Of Cellular And Molecular Biology, Institut for Healh Sciences Germans Trias i Pujol, 08916 - Badalona/ES

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 5840

Background

ROS1 fusions are found in 1% of lung cancer patients. EUCROSS is the first prospective European trial to evaluate crizotinib in this patient subset. Here we present an updated analysis of the progression-free survival (PFS), overall survival (OS) and molecular characteristics of progression.

Methods

Multi-centre, single arm phase II trial. Key eligibility criteria: ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearrangement. Treatment: 250 mg crizotinib BID. Key endpoints of this report: updated PFS (according to RECIST 1.1) and OS and molecular tumour characterization.

Results

Thirty patients were eligible for response evaluation (N = 30; intention-to-treat population, N = 34). Median follow-up was 44.9 months (95% CI, 39.6-47.4). At data-cut off 19 patients (63.3%) discontinued treatment due to progression or death. Investigator-assessed efficacy: ORR, 70% (95% CI, 51–85; 21/30); disease control rate, 90.0% (95% CI, 73.5-97.9; 27/30); median PFS, 19.4 months (95% CI, 10.1-31.2); 24-months-OS probability, 65.5% (95% CI, 48.3-82.9). Prevalence of co-occurring genetic aberrations by hybrid-capture sequencing was 61%. TP53 mutations were most frequent (28%; 5/18). PFS (p = 0.0219) and OS at 24 months (p = 0.015) were significantly shorter in TP53-mutant patients. Tissue or blood samples were collected in six patients at progression. In three (50%) samples, secondary mutations in ROS1 (i.e. p.G2032R (N = 2), p.L2026M (N = 1)) were detected. In one (17%), a PIK3CA mutation (p.E545K) was identified. In the other two patients (33%) aberrations of unknown significance were detected.

Conclusions

Updated PFS and OS results confirm the efficacy of crizotinib in ROS1-rearranged lung cancer patients. Patients with co-mutations in TP53 had significantly worse outcomes compared to TP53 wild-type patients. The most common mechanisms of resistance were mutations in ROS1. Next-generation ROS1 inhibitors or the multi-kinase inhibitor cabozantinib may be promising treatment options for these patients.

Clinical trial identification

NCT02183870.

Editorial acknowledgement

Legal entity responsible for the study

University Hospital of Cologne.

Funding

Pfizer.

Disclosure

S. Michels: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Boehringer Ingelheim; Research grant / Funding (institution): Janssen; Honoraria (self): Roche. B. Massuti Sureda: Honoraria (self): Merck Sharp Dome; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): Pfizer. H. Schildhaus: Honoraria (self): ZytoVision; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Novartis. M. Sebastian: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp Dome; Honoraria (self): Takeda; Honoraria (self): Mediolanum; Honoraria (self): AbbVie; Honoraria (self): Celgene. E. Felip: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Guardiant; Honoraria (self): Merck Sharp Dome; Honoraria (self): Merck KGa; Honoraria (self): Novartis. M. Reck: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca; Honoraria (self): Abbot; Honoraria (self): Celgene; Honoraria (self): Merck Sharp Dome; Honoraria (self): Merck KGa; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche. S. Merkelbach-Bruse: Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Roche; Honoraria (self), Research grant / Funding (institution): Novartis. L. Nogova: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Janssen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): Celgene. J. Wolf: Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Janssen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Chugay; Honoraria (self): Ignyta; Honoraria (self): Eli Lilly; Honoraria (self): Merck Sharp Dome; Honoraria (self): Roche. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.