MET exon 14 alteration defines a molecular subgroup of non-small cell lung cancer (NSCLC) for which MET inhibition with crizotinib is active reported Dr Alexander Drilon of the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in New York, NY, USA and colleagues in a letter published on 13 January 2020 in the Nature Medicine.
MET exon 14 alterations are oncogenic drivers of NSCLC. These alterations are associated with increased MET activity and preclinical sensitivity to MET inhibition. Crizotinib is a multikinase inhibitor with potent activity against MET.
The study team assessed antitumour activity and safety of crizotinib in 69 patients with advanced NSCLCs harbouring MET exon 14 alterations.
Objective response rate was 32% (95% confidence interval (CI), 21–45) among 65 patients evaluable for response. Objective responses were observed independent of the molecular heterogeneity that characterises these cancers and did not vary by splice-site region and mutation type of the MET exon 14 alteration, concurrent increased MET copy number or the detection of a MET exon 14 alteration in circulating tumour DNA.
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).
The authors concluded that the results of their study address an unmet need for targeted therapy in lung cancers with MET exon 14 alterations and add to an expanding list of genomically driven therapies for oncogenic subsets of NSCLC.
The study was supported by Pfizer.
Drilon A, Clark JW, Weiss J, et al. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat Med2020; 26:47–51. doi:10.1038/s41591-019-0716-8.