Crizotinib in MET-Deregulated or ROS1-Rearranged Pretreated Non-Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Lorenza Landi, Rita Chiari, Marcello Tiseo, Federica D'Inca, Claudio Dazzi, Antonio Chella, Angelo Delmonte, Laura Bonanno, Luca Bonanno, Diana Giannarelli, Diego Luigi Cortinovis, Filippo De Marinis, Gloria Borra, Alessandro Morabito, Cesare Gridelli, Domenico Galetta, Fausto Barbieri, Francesco Grossi, Enrica Capelletto, Gabriele MinutiFrancesca Mazzoni, Claudio Verusio, Emilio Bria, Greta Al, Rossella Bruno, Agnese Proietti, Gabriella Fontanini, Lucio Crino, Federico Cappuzzo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

47 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)7312-7319
Numero di pagine8
RivistaClinical Cancer Research
Volume25
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • crizotinib

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