The growing understanding of tumor genetic mechanisms and the development of molecular diagnostics have enabled the development of targeted therapies, leading to significant advances in the treatment of lung cancer [1]. The approval of selective MET inhibitors has expanded treatment options for patients with metastatic non-small cell lung cancer (NSCLC) and a MET tyrosine kinase receptor exon 14(METex14) skipping mutation [2, 3].
Approximately 80-90% of lung cancer cases are non-small cell lung cancer (NSCLC) [4]. Approximately 3-4% of these patients have a MET exon 14(METex14) skipping driver mutation [5]. This mostly affects patients over 70 years of age and is associated with a poor prognosis, partly because previous therapeutic approaches have had little effect [5-7].
TEPMETKO®: Selective oral, once-daily MET inhibitor[2].
TEPMETKO® is the only MET inhibitor approved in Switzerland that selectively inhibits the oncogenic signaling chain triggered by the MET mutation and is administered orally once daily [2, 3]*. Patients eligible for therapy with TEPMETKO® can be identified by screening based on next-generation sequencing. These are already performed as standard for mutations of comparable frequency, such as ALK [1, 4, 5]. NCCN guidelines already recommend TEPMETKO® as first-line therapy for metastatic NSCLC with a METex14 skipping mutation[8].
Rapid, consistent and sustained response [2].
The approval is based on the positive results of an interim analysis of the open-label phase II VISION trial [5]. This analysis evaluated pooled safety data from 448 patients (including 255 from the main VISION clinical trial) and efficacy data from 152 patients who received oral 450 mg of TEPMETKO® once daily. 45% of patients were treated with TEPMETKO® in the first line and 55% in the second or follow-up line. 10% of patients had stable brain metastases at baseline [2].
The primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC). Here, TEPMETKO® resulted in an ORR of 44.7%, independent of line of therapy(Table), patient age, type of prior therapies, and presence of brain metastases. Patients not only responded rapidly, typically within 6 weeks, but also showed a sustained response to TEPMETKO® with a median response duration of 11.1 months [2, 5]. Overall, TEPMETKO® was well tolerated, with grade ≥3 adverse effects occurring in 25.1% of patients and 10.6% discontinuing treatment prematurely [9].
Table: Results of the VISION study according to the Independent Review Committee (IRC) [2]. Overall response rate (ORR), median duration of response (mDOR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment with TEPMETKO®.
Conclusion
TEPMETKO® is the only once-daily selective therapy for metastatic NSCLC with METex14 skipping mutation*approved in Switzerland [2]. The oral MET inhibitor is already recommended by the NCCN guidelines as first-line therapy for this patient population [8]. The new selective therapy is a major advance for personalized medicine and underscores the importance of routine biomarker testing [1, 5].
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*The efficacy and safety of Tepmetko has not been studied in patients with additional oncogenic driver mutations including EGFR or ALK tumor aberrations [2].
METex14= mesenchymal-epithelial transition exon 14
With the financial support of Merck (Schweiz) AG.
CH-TEP-00051 05/2022
Brief technical information TEPMETKO®
Literature
Article online since 11.08.2021
