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

被引:159
作者
Landi, Lorenza [1 ]
Chiari, Rita [2 ]
Tiseo, Marcello [3 ]
D'Inca, Federica [4 ]
Dazzi, Claudio [1 ]
Chella, Antonio [5 ]
Delmonte, Angelo [6 ]
Bonanno, Laura [7 ]
Giannarelli, Diana [8 ]
Cortinovis, Diego Luigi [9 ]
de Marinis, Filippo [10 ]
Borra, Gloria [11 ]
Morabito, Alessandro [12 ]
Gridelli, Cesare [13 ]
Galetta, Domenico [14 ]
Barbieri, Fausto [15 ]
Grossi, Francesco [16 ]
Capelletto, Enrica [17 ]
Minuti, Gabriele [1 ]
Mazzoni, Francesca [18 ]
Verusio, Claudio [19 ]
Bria, Emilio [20 ,21 ]
Ali, Greta [22 ]
Bruno, Rossella [23 ]
Proietti, Agnese [22 ]
Fontanini, Gabriella [23 ]
Crino, Lucio [6 ]
Cappuzzo, Federico [1 ]
机构
[1] AUSL Romagna, Dipartimento Oncol & Ematol, Ravenna, Italy
[2] Osped Santa Maria Misericordia, Perugia, Italy
[3] Univ Parma & Oncol Med, Azienda Osped Univ Parma, Dipartimento Med & Chirurg, Parma, Italy
[4] Fdn Ric Traslaz, Rome, Italy
[5] Pneumol Univ, Dipartimento Cardiotorac Vasc, Osped Cisanello, Pisa, Italy
[6] IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, Italy
[7] Ist Oncol Veneto, Oncol Med 2, Padua, Italy
[8] IRCCS Regina Elena Natl Canc Inst, Rome, Italy
[9] Asst Osped San Gerardo, SS Lung Unit, SC Oncol Med, Monza, Italy
[10] Ist Europeo Oncol IRCSS, Thorac Oncol Div, Milan, Italy
[11] Osped Maggiore Novara, Novara, Italy
[12] Fdn G Pascale IRCCS, Ist Nazl Tumori, Naples, Italy
[13] Azienda Osped SG Moscati, Avellino, Italy
[14] IRCCS Oncol Giovanni Paolo II, Oncol Med Torac, Bari, Italy
[15] Azienda Osped Univ Policlin, Modena, Italy
[16] Fdn IRCCS Granda Osped Maggiore Policlin, Div Med Oncol, Milan, Italy
[17] Univ Torino, Dipartimento Oncol, Turin, Italy
[18] Azienda Osped Univ Careggi, SC Oncol Med, Florence, Italy
[19] PO Saronno, ASST Valleolona, Saronno, Italy
[20] Azienda Osped Univ Integrata, UO Oncol, Verona, Italy
[21] Univ Cattolica Sacro Cuore, Fdn Policlin Univ Agostino Gemelli IRCCS, Rome, Italy
[22] Azienda Osped Univ Pisana, Pisa, Italy
[23] Univ Pisa, Dipartimento Patol Chirurg Med Mol & Area Crit, Pisa, Italy
关键词
ROS1; REARRANGEMENTS; ADENOCARCINOMA; AMPLIFICATION; ALK; MUTATIONS; DEFINE;
D O I
10.1158/1078-0432.CCR-19-0994
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:7312 / 7319
页数:8
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