Crizotinib in MET-deregulated or ROS1-rearranged pretreated non–small cell lung cancer (METROS): A phase II, prospective, multicenter, two-arms trial: Clinical Cancer Research

L. Landi, R. Chiari, M. Tiseo, F. D'Inca, C. Dazzi, A. Chella, A. Delmonte, L. Bonanno, D. Giannarelli, D.L. Cortinovis, F. de Marinis, G. Borra, A. Morabito, C. Gridelli, D. Galetta, F. Barbieri, F. Grossi, E. Capelletto, G. Minuti, F. MazzoniC. Verusio, E. Bria, G. Al, R. Bruno, A. Proietti, G. Fontanini, L. Crino, F. Cappuzzo

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations. Patients and Methods: Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 >2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts. Results: From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2–30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0–5.8), and overall survival was 5.4 months (95% CI, 4.2–6.5). No difference in any clinical endpoint was observed between MET-amplified and exon 14–mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts. Conclusions: Crizotinib induces response in a fraction of MET-deregulated NSCLC. Additional studies and innovative therapies are urgently needed. © 2019 American Association for Cancer Research.
Original languageEnglish
Pages (from-to)7312-7319
Number of pages8
JournalClin. Cancer Res.
Volume25
Issue number24
DOIs
Publication statusPublished - 2019

Keywords

  • crizotinib
  • scatter factor receptor
  • adult
  • aged
  • anemia
  • Article
  • cancer pain
  • cohort analysis
  • coughing
  • drug mechanism
  • drug withdrawal
  • dyspnea
  • exon
  • fatigue
  • female
  • gene amplification
  • gene mutation
  • gene rearrangement
  • human
  • human tissue
  • hypertransaminasemia
  • major clinical study
  • male
  • MET gene
  • multicenter study
  • multiple cycle treatment
  • nausea
  • neutropenia
  • non small cell lung cancer
  • oncogene
  • overall survival
  • peripheral edema
  • phase 2 clinical trial
  • priority journal
  • progression free survival
  • prospective study
  • ROS1 gene
  • treatment response
  • visual disorder

Fingerprint

Dive into the research topics of 'Crizotinib in MET-deregulated or ROS1-rearranged pretreated non–small cell lung cancer (METROS): A phase II, prospective, multicenter, two-arms trial: Clinical Cancer Research'. Together they form a unique fingerprint.

Cite this