+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Antitumor Activity of Crizotinib in Lung Cancers Harboring a MET Exon 14 Alteration


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          MET exon 14 alterations are oncogenic drivers of non-small cell lung cancers (NSCLCs). 1 These alterations are associated with increased MET activity and preclinical sensitivity to MET inhibition. 2 Crizotinib is a multikinase inhibitor with potent activity against MET. 3 The antitumor activity and safety of crizotinib were assessed in 69 patients with advanced NSCLCs harboring MET exon 14 alterations in an expansion cohort of an open-label phase 1 study of crizotinib ( NCT00585195). The confirmed objective response rate was 32% (95% confidence interval [CI], 21–45) among 65 response-evaluable patients. Objective responses were observed independent of the molecular heterogeneity that characterizes these cancers and did not vary by MET exon 14 alteration splice site region and mutation type, concurrent increased MET copy number, or the detection of a MET exon 14 alteration in ctDNA. The median duration of response was 9.1 months (95% CI, 6.4–12.7). The median progression-free survival was 7.3 months (95% CI, 5.4–9.1). MET exon 14 alteration defines a molecular subgroup of NSCLCs for which MET inhibition with crizotinib is active. These results address an unmet need for targeted therapy in patients with MET exon 14-altered lung cancers and adds to an expanding list of genomically-driven therapies for oncogenic subsets of NSCLC.

          Related collections

          Most cited references44

          • Record: found
          • Abstract: found
          • Article: not found

          Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer

          Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).
            • Record: found
            • Abstract: found
            • Article: not found

            Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC

            The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy.
              • Record: found
              • Abstract: not found
              • Article: not found

              Toxicity and response criteria of the Eastern Cooperative Oncology Group.


                Author and article information

                Nat Med
                Nat Med
                Nature medicine
                6 December 2019
                13 January 2020
                January 2020
                08 October 2021
                : 26
                : 1
                : 47-51
                [1 ]Memorial Sloan Kettering Cancer Center, New York, NY, USA.
                [2 ]Massachusetts General Hospital, Boston, MA, USA.
                [3 ]Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
                [4 ]University of California Irvine School of Medicine, Orange, CA, USA.
                [5 ]University of Colorado, Denver, CO, USA.
                [6 ]Peter MacCallum Cancer Centre, Melbourne, Australia.
                [7 ]Ohio State University, Columbus, OH, USA.
                [8 ]University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA.
                [9 ]Dana Farber Cancer Institute, Boston, MA, USA.
                [10 ]Hyogo Cancer Center, Akashi, Japan.
                [11 ]Aichi Cancer Center, Nagoya, Japan.
                [12 ]Kindai University, Osaka, Japan.
                [13 ]Pfizer Oncology, La Jolla, CA, USA.
                [14 ]Pfizer Oncology, Milan, Italy.
                Author notes

                Equal Contributions Statement

                Not applicable


                A.D. wrote the first draft of the paper and served as an investigator on the study. J.W.C., J.W., S-H.I.O., D.R.C., B.J.S., G.A.O., L.C.V., G.J.R., R.S.H, G.I.S, M.S., T.H., H.H. and P.K.P served as investigators on the study and wrote the paper. M.M.A. and K.D.W. wrote the paper. D.A.M., S.C.W., S.L. and T.U. analyzed the data and wrote the paper.

                Corresponding Author: Correspondence to Alexander Drilon at Memorial Sloan Kettering Cancer Center, 885 2 nd Ave., New York, NY 10065, or at drilona@ 123456mskcc.org .

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms




                Comment on this article