Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis
| Autor: | Yoko Korenaga Fukuda, Jeffrey W. Clark, Shirish M. Gadgeel, Pasi A. Jänne, Patrick M. Forde, Giulia Costanza Leonardi, Sasha Kravets, Viola W. Zhu, Daniel B. Costa, Lynette M. Sholl, Sai-Hong Ignatius Ou, D. Ross Camidge, Rebecca S. Heist, Suzanne E. Dahlberg, Tony Mok, Alexander Drilon, Mark M. Awad, Sinead A. Noonan, Conor E. Steuer |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology Adult Male Cancer Research medicine.medical_specialty Lung Neoplasms Population Antineoplastic Agents Article 03 medical and health sciences Exon 0302 clinical medicine Crizotinib Internal medicine Carcinoma Non-Small-Cell Lung medicine Retrospective analysis Humans Lung cancer education Protein Kinase Inhibitors Aged Retrospective Studies Aged 80 and over education.field_of_study Proportional hazards model business.industry Hazard ratio High-Throughput Nucleotide Sequencing Exons Middle Aged Proto-Oncogene Proteins c-met medicine.disease Survival Analysis 030104 developmental biology 030220 oncology & carcinogenesis Mutation Female Non small cell business medicine.drug |
| Zdroj: | Lung Cancer |
| ISSN: | 1872-8332 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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