Author: By Laura Cowen, medwireNews Reporter
medwireNews: Around half of patients with advanced or metastatic non-small-cell lung cancer (NSCLC) with a confirmed MET exon 14 skipping mutation respond to treatment with the highly selective MET inhibitor tepotinib, show results from the phase II VISION trial.
Writing in The New England Journal of Medicine, Paul Paik (Memorial Sloan Kettering Cancer Center, New York, USA) and co-authors say their 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.”
They add that the study results, which were also presented at the virtual 2020 ASCO Annual Meeting, “led to regulatory approval of tepotinib and its companion diagnostic assay for the detection of MET alterations (ArcherMET CDx) in March 2020 in Japan.”
At the time of data analysis, 152 patients had received oral tepotinib 500 mg once daily. Of these, 99 (median age 74 years), had at least 9 months of follow-up (median 17.4 months) and were eligible for efficacy analysis.
In this group, the objective response rate by independent review was 46%, with a median response duration of 11.1 months.
The response rate was 48% among the 66 patients whose mutation status was determined by liquid biopsy and 50% among the 60 patients assessed by tissue biopsy. Of note, 27 patients were tested for MET mutation status by both methods.
The median duration of progression-free survival (PFS) was 8.5 months and the median overall survival (OS) was 17.1 months, but the researchers note that the OS data are not yet mature.
Eleven patients had brain metastases at baseline, none of which qualified to be defined as target lesions according to RECIST. The response rate by independent review in these patients was 55%, with a median response duration of 9.5 months and a median PFS duration of 10.9 months.
Molecular analysis of 51 paired liquid biopsy samples taken at baseline and during treatment showed that 67% had a molecular circulating free DNA response to tepotinib. This was defined as clearance of more than 75% of MET exon alterations in circulating free DNA.
The researchers also assessed patient-reported quality of life and found global functioning and symptoms of dyspnoea and chest pain to be stable throughout treatment, while cough symptoms were reduced.
The researchers say that the adverse event profile of tepotinib was similar to that previously reported. Treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 27% of the 152 patients in the full cohort, most commonly peripheral oedema (7%).
One-third of patients had a TRAE that led to a dose reduction and 11% discontinued treatment permanently due to a TRAE. The most common reasons for dose reductions or discontinuations were peripheral oedema, pleural effusion and dyspnoea. There was one treatment-related death, in a patient with respiratory failure and dyspnoea, secondary to interstitial lung disease.
Paul Paik and co-authors conclude that their results “compare favorably with results from other studies of investigational MET inhibitors involving patients with NSCLC who had MET exon 14 skipping mutations.”
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group
References
Paik PK, Felip E, Veillon, R, et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med; Advance online publication 29 May 2020. doi: 10.1056/NEJMoa2004407
Link
https://www.nejm.org/doi/10.1056/NEJMoa2004407
Paik PK, Horn L, Kowalski DM, et al. Tepotinib in patients (pts) with NSCLC with MET exon 14 (METex14) skipping: Health-related quality of life (HRQoL). J Clin Oncol 38: 2020 (suppl; abstr 9575).
Link
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group