Capmatinib successfully overcomes tepotinib‐induced intolerable peripheral edema

Kunimasa, Kei; Kawamura, Takahisa; Tamiya, Motohiro; Inoue, Tomio; Kuhara, Hanako; Nishino, Kazumi; Kumagai, Toru

doi:10.1111/1759-7714.14205

Cited by 7 publications

(4 citation statements)

References 8 publications

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“…MET inhibitors, which act on the HGF/MET signaling pathway, would disrupt this balance and lead to increased fluid leakage. 29 Our study also supported the possibility of this conjecture that type 1b MET TKI (savolitinib), with higher specificity, has a higher incidence of peripheral edema than type 1a MET TKI (crizotinib).…”

Section: Discussionsupporting

confidence: 85%

Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

et al. 2023

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Background The c‐MET protein, encoded by the mesenchymal‐epithelial transition factor (MET) gene, can regulate cell proliferation, migration and invasion. Studies have shown that it is one of the essential driver genes for non‐small cell lung cancer (NSCLC). Currently, several clinical studies have carried out objective assessments on the efficacy and safety of different types of MET tyrosine kinase inhibitors (TKIs). However, direct cross‐sectional comparisons between different agents are still not available. Methods Our study was a single‐center retrospective clinical study, which collected the data from MET positive NSCLC patients treated with MET TKIs at the Lung Cancer Center of Peking Union Medical College Hospital. We explored the efficacy and safety of crizotinib versus savolitinib in patients with METex14 skipping and MET amplification, separately. Results Patients with METex14 skipping (median PFS = 10.7 months) had a better clinical response to MET TKIs than MET amplification patients (median PFS = 4.1 months). In the METex14 skipping subgroup, savolitinib did not show better survival benefit with significance than crizotinib (p > 0.05). In the MET amplification subgroup, savolitinib (median PFS = 7.1 months) demonstrated a better progression‐free survival benefit than crizotinib (median PFS = 1.4 months), p = 0.05. The most common adverse effects of both MET TKIs were peripheral edema (41.2%), gastrointestinal reactions (23.5%), and liver injury (14.7%). The incidence rate of peripheral edema was higher in savolitinib than crizotinib. Conclusion In METex14 skipping NSCLC patients, the efficacy of savolitinib and crizotinib did not show significant difference. In MET amplification patients, savolitinib showed better efficacy than crizotinib.

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Section: Discussionsupporting

confidence: 85%

Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

et al. 2023

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“… 8 , 14 , 15 In addition, a case of tepotinib leading to intolerable peripheral edema in the patient was reported; however, MET inhibitor could be continued by switching to capmatinib. 16 In our study, the rate of peripheral edema is relatively low. Therefore, different MET inhibitors may lead to quite different AEs.…”

Section: Discussionmentioning

confidence: 47%

Phase 1 Study of the Selective c-MET Inhibitor, HS-10241, in Patients With Advanced Solid Tumors

Dong¹,

Li²,

Chen³

et al. 2023

JTO Clinical and Research Reports

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“…Some reports showed MET pathway inhibitors and certain tyrosine kinase inhibitors (TKIs) like rilotumumab and onartuzumab also caused peripheral swelling 13 , 14 . The etiology is unknown but may be due to attenuated hepatocyte growth factor (HGF)/MET signaling in vascular endothelium, disrupting the balance and leading to leakage 15 , 16 . Therefore, early and vigilant monitoring such as weighing is recommended, which can reduce complications from managing late edema, especially in susceptible populations.…”

Section: Discussionmentioning

confidence: 99%

A real-world pharmacovigilance study of FDA adverse event reporting system events for Capmatinib

Qi,

Li,

Lin

et al. 2024

Sci Rep

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Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib.

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Capmatinib successfully overcomes tepotinib‐induced intolerable peripheral edema

Cited by 7 publications

References 8 publications

Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

Savolitinib versus crizotinib for treating MET positive non‐small cell lung cancer

Phase 1 Study of the Selective c-MET Inhibitor, HS-10241, in Patients With Advanced Solid Tumors

A real-world pharmacovigilance study of FDA adverse event reporting system events for Capmatinib

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