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Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase II clinical trial–Updated report on progression-free and overall survival.
Journal article

Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase II clinical trial–Updated report on progression-free and overall survival.

  • Michels, Sebastian Yves Friedrich Lung Cancer Group Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Dept. for Internal Medicine, Cologne, Germany;
  • Franklin, Jeremy Institute of Medical Statistics and Computational Biology, University Hospital Cologne, Cologne, Germany;
  • Massuti, Bartomeu Alicante University Hospital ISABIAL, Alicante, Spain;
  • Sebastian, Martin University Hospital of Frankfurt, Frankfurt, Germany;
  • Schildhaus, Hans-Ulrich Institute of Pathology, University Hospital Essen, Essen, Germany;
  • Felip, Enriqueta Vall d´Hebron University Hospital, Barcelona, Spain;
  • Grohe, Christian Department for Pneumology, Berlin Evangelical Lung Clinic, Berlin, Germany;
  • Rodriguez-Abreu, Delvys Hospital Universitario Insular de Gran Canaria, Las Palmas De Gran Canaria, Spain;
  • Bischoff, Helge Thoraxonkologie, Thoraxklinik, Heidelberg, Germany;
  • Carcereny, Enric Medical Oncology Department. Catalan Institute of Oncology, Hospital Germans Trias i Pujol, B.ARGO GROUP Badalona Applied Research Group in Oncology, Badalona, Spain;
  • Corral, Jesús Department of Oncology. Clínica Universidad de Navarra, Pamplona, Spain;
  • Dingemans, Anne-Marie C. Maastricht University Medical Center, Maastricht, Netherlands;
  • Insa, Amelia Hospital Clinico Universitario de Valencia, Valencia, Spain;
  • Reck, Martin LungenClinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany;
  • Rothschild, Sacha Medical Oncology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland;
  • Smit, Egbert F. Vrije Universiteit VU Medical Centre, Amsterdam, Netherlands;
  • Provencio, Mariano Hospital Universitario Puerta de Hierro, Majadahonda, Spain;
  • Büttner, Reinhard University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute of Pathology, Cologne, Germany;
  • Rosell, Rafael Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain and Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain and Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, Badalona, Barcelona, Spain;
  • Wolf, Juergen Lung Cancer Group Cologne, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Dept. for Internal Medicine, Cologne, Germany;
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Published in:
  • Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. 9066-9066
Cancer Research
Oncology
English 9066 Background: ROS1 rearrangements are found in 1% of non-small cell lung cancer (NSCLC) patients. Early clinical trials in the US and East Asia have proven the therapeutic efficacy of crizotinib in this subset of patients. EUCROSS is the first prospective European trial to evaluate the acitivity of crizotinib in ROS1-positive lung cancer. Here we present an updated analysis of the investigator-assessed progression-free survival (PFS) and overall survival (OS). Methods: EUCROSS is a multi-centre, single arm phase 2 trial (NCT02183870). Key eligibility criteria: ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation). Treatment with crizotinib was initiated at a dose of 250 mg twice daily. Primary endpoint of the trial: investigator-assessed objective response rate (ORR) in the response-evaluable population (Response Evaluation Criteria in Solid Tumors, version 1.1). Key endpoints of this report: updated PFS and OS and updated molecular characterization of tumour tissue. Results: Thirty-four patients received treatment with crizotinib and were included in the intention-to-treat analysis. Four patients were excluded from the primary endpoint analysis due to violation of eligibility criteria (response-evaluable set, N = 30). Median follow-up period was 44.9 months. At the time of data cut-off for this report 19 patients (63%) discontinued treatment due to progression or death. Investigator ORR was 70% (95% CI, 51–85; 21/30), disease control rate was 90% (95% CI, 73.5-97.9; 27/30) and median PFS was 19.4 months (95% CI, 10.1-31.2). Median OS was not reached, but 24-months-OS probability was 66% (95% CI, 48.3-82.9). Tissue of 18 patients was available for hybrid-capture-based sequencing. Co-occurring genetic aberrations were found in 61% (11/18). TP53 mutations were most frequent (28%; 5/18). PFS (24-months probability, TP53-mut. 0% vs. TP53 wild-type (wt) 61%; p = 0.0219) and OS (24-months, TP53-mut. 40% vs. TP53 wt 83%; p = 0.015) were significantly shorter in TP53-mutant patients. Differences in OS and PFS stratified by number of prior treatment lines (0-1 vs. > = 2), brain metastases (yes vs. no) or CD74-rearrangement ( CD74- ROS1 vs. other fusion type) status were not significant. Conclusions: Updated PFS and OS results show that crizotinib is highly effective in ROS1-rearranged lung cancer. Co-occurring TP53 mutations were associated with a significantly worse outcome. Clinical trial information: NCT02183870.
Language
  • English
Open access status
closed
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Persistent URL
https://folia.unifr.ch/global/documents/183545
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