Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis

Mark M. Awad, Giulia C. Leonardi, Sasha Kravets, Suzanne E. Dahlberg, Alexander Drilon, Sinead A. Noonan, D. Ross Camidge, Sai Hong I. Ou, Daniel B. Costa, Shirish M. Gadgeel, Conor E. Steuer, Patrick M. Forde, Viola W. Zhu, Yoko Fukuda, Jeffrey W. Clark, Pasi A. Jänne, Tony Mok, Lynette M. Sholl, Rebecca S. Heist

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Although dramatic responses to MET inhibitors have been reported in patients with MET exon 14 (METex14) mutant non-small cell lung cancer (NSCLC), the impact of these treatments on overall survival in this population is unknown. Methods: We conducted a multicenter retrospective analysis of patients with METex14 NSCLC to determine if treatment with MET inhibitors impacts median overall survival (mOS). Event-time distributions were estimated using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox models were fitted to estimate hazard ratios. Results: We identified 148 patients with METex14 NSCLC; the median age was 72; 57% were women and 39% were never smokers. Of the 34 metastatic patients who never received a MET inhibitor, the mOS was 8.1 months; those in this group with concurrent MET amplification had a trend toward worse survival compared to cancers without MET amplification (5.2 months vs 10.5 months, P = 0.06). Of the 27 metastatic patients who received at least one MET inhibitor the mOS was 24.6 months. A model adjusting for receipt of a MET inhibitor as first- or second-line therapy as a time-dependent covariate demonstrated that treatment with a MET inhibitor was associated with a significant prolongation in survival (HR 0.11, 95% CI 0.01-0.92, P = 0.04) compared to patients who did not receive any MET inhibitor. Among 22 patients treated with crizotinib, the median progression-free survival was 7.4 months. Discussion: For patients with METex14 NSCLC, treatment with a MET inhibitor is associated with an improvement in overall survival.

Original languageEnglish (US)
Pages (from-to)96-102
Number of pages7
JournalLung Cancer
Volume133
DOIs
StatePublished - Jul 2019

Keywords

  • MET exon 14
  • NSCLC
  • Overall survival
  • TKI

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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