About one-half of patients with non-small cell lung cancer (NSCLC) and a confirmed MET exon 14-skipping mutation experienced partial response of their disease with the use of MET inhibitor tepotinib, according to the results of a phase 2 study.1 MET exon 14-skipping mutation occurs in about 3% to 4% of patients with NSCLC.

The study included 152 patients who received 500 mg tepotinib once daily. The primary endpoint was objective response by independent review among the 99 patients who had at least 9 months of follow-up.

A little less than one-half (46%) of patients had a response, according to the independent review. Median duration of response was 11.1 months. Among the 66 patients in the liquid-biopsy group, 48% had a response; among the 60 patients in the tissue-biopsy group, 50% had a response.

The response rate by investigator assessment varied from 56% to 62% based on biopsy type. Almost 90% of patients experienced tumor shrinkage. According to the researchers, onset of response was mostly within 6 weeks of initiation of therapy.


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“These results compare favorably with results from other studies of investigational MET inhibitors involving patients with NSCLC who had MET exon 14 skipping mutations,” the researchers wrote.

Median duration of progression-free survival by independent review was 8.5 months in the combined-biopsy group. More than one-third (35%) of patients had discontinued tepotinib at data cutoff and received subsequent treatment. The median duration of overall survival was 17.1 months; however, these data are not yet mature.

“These findings validate MET exon 14 skipping mutations as bona fide therapeutic targets and underscore the importance of routine testing for these MET alterations by means of liquid or tissue biopsy,” the researchers concluded.

Reference

Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations [published online May 29, 2020]. N Engl J Med. doi: 10.1056/NEJMoa2004407