VISION: Tepotinib promising for MET exon 14-mutated advanced NSCLC
medwireNews: Individuals with advanced non-small-cell lung cancer (NSCLC) positive for MET exon 14 skipping mutations could benefit from treatment with the selective MET inhibitor tepotinib, suggests a phase 2 trial.
The VISION data were simultaneously presented at the virtual 2020 ASCO Annual Meeting and published in The New England Journal of Medicine.
During a median follow-up of 17.4 months, once-daily treatment with oral tepotinib 500 mg led to an independently-assessed objective response rate (ORR) of 46.5% among the 99 participants with locally advanced or metastatic disease who had been followed up for a minimum of 9 months at data cutoff.
All responses were partial and lasted for a median of 11.1 months. Median progression-free survival was 8.5 months and the overall survival data were not mature.
In all, 43 patients were treatment-naïve, while the remaining 56 had received at least one prior line of therapy, but the ORRs by independent review were comparable to that of the overall cohort, at 44.2% and 48.2%, respectively. This was also the case for most other subgroups, with the largest difference seen for patients with versus without a smoking history, for whom the respective ORRs were 56.5% and 35.6%.
The investigators explain that the presence of MET exon 14 skipping mutations was detected by liquid biopsy in 66 participants and by tumor biopsy in 60, while 27 participants had positive results by both methods. But again, the results were similar regardless of the detection method, with ORRs of 48.5% and 50.0% for the liquid versus tissue biopsy subgroups.
“The adverse-event profile reported here was similar to those in previous studies of tepotinib, with a low frequency of treatment discontinuation,” write Paul Paik (Memorial Sloan Kettering Cancer Center, New York, USA) and co-researchers.
Specifically, treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 28% of patients, with peripheral edema the most frequent event. A total of 33% of participants required a dose reduction due to a TRAE and 11% discontinued permanently. One death was attributed to the study drug.
Noting that peripheral edema has been observed with other agents targeting the MET pathway, the authors say: “Proactive monitoring for peripheral edema is recommended and can be managed with temporary discontinuation of tepotinib or dose reduction.”
They also report on health-related quality of life over 24 weeks, which “was maintained during receipt of tepotinib.” For instance, the mean reduction from baseline in the EORTC QLQ-LC13 cough symptom score exceeded the predefined threshold of a clinically meaningful difference, while scores for dyspnea and chest pain stayed stable. And similarly, the scores for global functioning on the EORTC QLQ-C30 scale also remained stable.
The researchers conclude that the VISION study shows “durable clinical activity” of tepotinib in this patient population.
They add: “Results from this study have led to regulatory approval of tepotinib and its companion diagnostic assay for the detection of MET alterations (ArcherMET CDx) in March 2020 in Japan.”
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