Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations

Ahn, Myung‐Ju; Mendoza, Michael Antonio F.; Pavlakis, Nick; Kato, Terufumi; Soo, Ross A.; Kim, Dong-Wan; Liam, Chong Kin; Hsia, Te‐Chun; Lee, Chee Khoon; Reungwetwattana, Thanyanan; Geater, Sarayut Lucien; Chan, Oscar S.H.; Prasongsook, Naiyarat; Solomon, Benjamin; Nguyen, Thi Thai Hoa; Kozuki, Toshiyuki; Yang, James Chih‐Hsin; Wu, Yang‐Chang; Mok, T.; Tan, Daniel; Yatabe, Yasushi

doi:10.1016/j.cllc.2022.07.012

Cited by 10 publications

(20 citation statements)

References 76 publications

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“…Although both LBx and TBx can be used for detecting METex14 skipping, the analysis derived from TBx may be more commonly used and accepted. 20 Our results…”

Section: Efficacy By Metex14 Skipping Detection Methodsmentioning

confidence: 63%

Long‐term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study

Morise,

Kato,

Matsumoto

et al. 2024

Cancer Science

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Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non–small‐cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression‐free survival (PFS), overall survival (OS), and safety. Here we report the analysis of the efficacy and safety of tepotinib in all Japanese patients with advanced METex14 skipping NSCLC from VISION (n = 38) with >18 months' follow‐up. The median age of the Japanese patients was 73 years (range 63–88), 39.5% of patients were ≥75 years old, 68.4% were male, 55.3% had a history of smoking, 76.3% had adenocarcinoma, and 10.5% of patients had known brain metastases at baseline. Overall, the objective response rate (ORR) was 60.5% (95% confidence interval (CI): 43.4, 76.0) with a median DOR of 18.5 months (95% CI: 8.3, not estimable). ORR in treatment‐naïve patients (n = 18) was 77.8% (95% CI: 52.4, 93.6), and in patients aged ≥75 years (n = 15), ORR was 73.3% (95% CI: 44.9, 92.2). The most common treatment‐related adverse event (AE) with any grade was blood creatinine increase (65.8%), which resolved following tepotinib discontinuation. Other common treatment‐related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION.

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“…Although both LBx and TBx can be used for detecting METex14 skipping, the analysis derived from TBx may be more commonly used and accepted. 20 Our results…”

Section: Efficacy By Metex14 Skipping Detection Methodsmentioning

confidence: 63%

Long‐term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study

Morise,

Kato,

Matsumoto

et al. 2024

Cancer Science

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“…Smoking status is not associated with the presence of MET exon 14 skipping. The median age of patients (> 70 years) is higher than in the case of other oncogene‐driven tumours 64,65,67 …”

Section: Molecular‐targeted Drugs For Driver Mutationsmentioning

confidence: 99%

“…To select patients with this alteration, RNA-based assays are recommended because of a high variability of mutations and indels, several of which cannot be detected with DNA-based assays. 64,65 Clinicopathologically, adenocarcinomas are the most common histological type, but squamous-cell carcinomas and other types of NSCLCs harbour this alteration, and it is particularly enriched in sarcomatoid carcinoma (5-32%). 66,67 Smoking status is not associated with the presence of MET exon 14 skipping.…”

Section: E T E X O N 1 4 S K I P P I N Gmentioning

confidence: 99%

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Molecular pathology of non‐small cell carcinoma

Yatabe

2023

Histopathology

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Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large‐scale sequencing studies, translational research and new drug development, which has promoted our understanding of the molecular pathology of lung cancer. According to the driver alterations, different characteristics have been revealed, such as differences in ethnic prevalence, median age and alteration patterns. Consequently, beyond traditional chemoradiotherapy, molecular‐targeted therapy and treatment with immune check‐point inhibitors (ICI) also became available major therapeutic options. Interestingly, clinical results suggest that the recently established therapies target distinct lung cancer proportions, particularly between the EGFR/ALK and PD‐1/PD‐L1‐positive subsets, e.g. the kinase inhibitors target driver mutation‐positive tumours, whereas driver mutation‐negative tumours respond to ICI treatment. These therapeutic efficacy‐related differences might be explained by the molecular pathogenesis of lung cancer. Addictive driver mutations promote tumour formation with powerful transformation performance, resulting in a low tumour mutation burden, reduced immune surveillance, and subsequent poor response to ICIs. In contrast, regular tobacco smoke exposure repeatedly injures the proximal airway epithelium, leading to accumulated genetic alterations. In the latter pathway, overgrowth due to alteration and immunological exclusion against neoantigens is initially balanced. However, tumours could be generated from certain clones that outcompete immunological exclusion and outgrow the others. Consequently, this cancer type responds to immune check‐point treatment. These pathogenic differences are explained well by the two‐compartment model, focusing upon the anatomical and functional composition of distinct cellular components between the terminal respiratory unit and the air‐conducting system.

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“…Hence, when exon 14 is skipped, CBL-mediated degradation of the MET protein is impaired, resulting in excess MET activity [ 2 ]. In Japan, two MET inhibitors have recently been approved for patients with advanced NSCLC harboring MET exon 14 skipping mutations [ 3 ]. However, clinical trials have shown that more than 50% of these patients experience early relapse within 12 months owing to acquired resistance to these inhibitors [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Durable Response to Chemoimmunotherapy of a Lung Adenocarcinoma Harboring a MET Exon 14 Skipping Mutation

Nitta¹,

Morimoto²,

Tani³

et al. 2023

Cureus

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Chemoimmunotherapy is the first-line standard treatment for patients with non-small cell lung cancer (NSCLC). However, there are few reports on the efficacy of chemoimmunotherapy in patients with NSCLC who harbor the MET exon 14 skipping mutation. We report the case of an 81-year-old male patient with lung adenocarcinoma with a MET exon 14 skipping mutation who was treated with chemoimmunotherapy and achieved a durable response. Chemoimmunotherapy may be a promising treatment option for patients with a MET exon 14 skipping mutation. However, further studies are needed to characterize the objective response rate and response duration in these populations.

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Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations

Cited by 10 publications

References 76 publications

Long‐term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study

Long‐term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study

Molecular pathology of non‐small cell carcinoma

Durable Response to Chemoimmunotherapy of a Lung Adenocarcinoma Harboring a MET Exon 14 Skipping Mutation

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