MET Exon 14 Skipping in NSCLC: A Systematic Literature Review of Epidemiology, Clinical Characteristics, and Outcomes

Vioix, H.; Pfeiffer, Boris M; Campden, Rhiannon I.; Chen, N.; Heeg, Bart; Cortot, A.

doi:10.1016/j.cllc.2023.06.008

Cited by 22 publications

(10 citation statements)

References 69 publications

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“…In this retrospective study, the occurrence rate of MET ex14 skipping in NSCLC was statistically determined to be 4%, similar to what was previously reported [ 13 , 14 ]. However, the potential influence of variant occurrence rates across different ethnicities must be considered, increasing the difficulty in definitively addressing concerns regarding false positives generated by the Oncomine ™ Focus Assay.…”

Section: Discussionsupporting

confidence: 88%

Retrospective Analysis to Optimize the Detection of MET Exon 14 Skipping Mutations in Non-Small Cell Lung Cancer

Lu,

Tsai,

Lin

et al. 2024

Diagnostics

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Our study optimized METex14 skipping mutation detection by analyzing 223 Oncomine™ Focus Assay-positive cases using Pan Lung Cancer PCR Panel and reverse transcription (RT)-PCR. Among the 11 METex14 skipping mutation-positive cases (average read counts: 1390), 2 with Oncomine™ Focus Assay read counts of 2540 and 10,177 were positive on all platforms. Those with Oncomine™ Focus Assay read counts ranging from 179 to 612 tested negative elsewhere. Specimens with low ratios (average ratio: 0.12% for nine cases) may yield false-positive results. Our results suggested that monitoring read counts and ratios and validating the results with RT-PCR are crucial to prevent false positives.

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Section: Discussionsupporting

confidence: 88%

Retrospective Analysis to Optimize the Detection of MET Exon 14 Skipping Mutations in Non-Small Cell Lung Cancer

Lu,

Tsai,

Lin

et al. 2024

Diagnostics

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“…VISION is the largest clinical trial to date in patients with MET ex14 skipping. Given the poor prognosis [ 33 ], limited efficacy of standard of care therapies in these patients [ 34 ], and the rarity of the alteration [ 35 ], the durable clinical benefit shown by tepotinib in this single-arm trial has provided strong evidence to support its approval in many countries globally, including several in Asia. In countries such as the US, where tepotinib was granted conditional approval based on initial results from VISION, subsequent data from the study is being used to fulfill post-marketing requirements by providing more mature results in a larger patient cohort [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION

Kato,

Yang,

Ahn

et al. 2024

Br J Cancer

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Background Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022). Methods Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily. Primary endpoint: objective response (RECIST 1.1) by independent review. Secondary endpoints included: DOR, progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life (HRQoL). Results Across treatment lines in 106 Asian patients (39.6% female, 43.4% smoking history, 79.2% adenocarcinoma, 47.2% treatment-naive), ORR was 56.6% (95% CI: 46.6, 66.2), mDOR 18.5 months (10.4, ne), mPFS 13.8 months (10.8, 22.0), and mOS 25.5 months (19.3, 36.4). Consistent efficacy observed, regardless of baseline characteristics. HRQoL remained stable during treatment. Treatment-related adverse events (TRAEs) occurred in 95.3% of patients (39.6% Grade ≥3). Most common TRAEs: peripheral edema (62.3%), creatinine increase (38.7%). Conclusions Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian patients with METex14 skipping NSCLC. Clinical trial registration NCT02864992

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“…However, the effectiveness of chemotherapy is generally constrained in advanced or metastatic NSCLC, particularly in patients with MET exon 14 skipping mutations. 7 In addition, immunotherapy has demonstrated limited efficacy in individuals with MET alterations. 8 – 11 Consequently, there is a compelling need to explore novel treatment modalities with enhanced efficacy for these patients.…”

Section: Discussionmentioning

confidence: 99%

Assessment of efficacy and safety of MET tyrosine kinase inhibitors in non-small-cell lung cancer patients with MET alterations

Wang,

Xu,

Wang

et al. 2024

Ther Adv Med Oncol

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Background: While targeted therapy has become the standard treatment for certain non-small-cell lung cancer (NSCLC) patients with gene mutation positivity, there remains a lack of enough reports of the efficacy of mesenchymal–epithelial transition (MET) alterations in the real world. Objectives: We aimed to explore the efficacy and toxicity of targeted therapy in NSCLC patients with different types of MET alterations and hope to provide more clinical medication guidance. Design: Designed different subgroups to compare the efficacy and safety of targeted therapy in NSCLC patients with MET alterations. Methods: We conducted analyses on the efficacy and safety of mesenchymal–epithelial transition factor-tyrosine kinase inhibitor (MET-TKI) therapy in NSCLC patients with MET alterations. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 criteria, and both progression-free survival (PFS) and overall survival were determined using the Kaplan–Meier method. Results: Our study encompassed 116 NSCLC patients with MET alterations, including MET ex14 skipping mutation ( n = 50), MET primary amplification (amp) ( n = 25), and secondary amp ( n = 41). Among treated patients, 34 achieved a partial response, while 52 exhibited stable disease. The overall response rate for the entire cohort was 29.31%, with a disease control rate of 74.14%. A significant difference was observed in the median PFS among patients with MET ex14 skipping mutation, MET primary amplification (amp), and secondary amp (10.4 versus 6.6 versus 4.5 months, p = 0.002). In all, 69 patients experienced drug-related adverse effects, with the most common being peripheral edema (35.34%), nausea and vomiting (21.55%), and fatigue (10.34%). In total, 29 patients (25%) encountered drug-related adverse reactions of grade 3 or higher. Conclusion: MET-TKI therapy works better for MET ex14 skipping mutation than other types of MET gene alteration. In the two MET amplified groups, the secondary amp was less effective. This study may provide more research support for the treatment of these patients.

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MET Exon 14 Skipping in NSCLC: A Systematic Literature Review of Epidemiology, Clinical Characteristics, and Outcomes

Cited by 22 publications

References 69 publications

Retrospective Analysis to Optimize the Detection of MET Exon 14 Skipping Mutations in Non-Small Cell Lung Cancer

Retrospective Analysis to Optimize the Detection of MET Exon 14 Skipping Mutations in Non-Small Cell Lung Cancer

Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION

Assessment of efficacy and safety of MET tyrosine kinase inhibitors in non-small-cell lung cancer patients with MET alterations

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