capmatinib
Sources réglementaires consultées
Indications approuvées
- Chez l’adulte atteint d’un cancer bronchique non à petites cellules métastatique dont la tumeur présente une mutation entraînant le saut de l’exon 14 de MET, détectée par un test approuvé par la FDA.
Mises en garde cliniques
- Mise en garde majeure · La pneumopathie interstitielle ou pneumonite peut être fatale. Surveiller toute dyspnée, toux ou fièvre nouvelle ou aggravée ; suspendre immédiatement en cas de suspicion et arrêter définitivement en l’absence d’autre cause. — DailyMed, TABRECTA set_id 455892c3-d144-4ba8-9ab4-79cabff9876d
- Mise en garde majeure · Contrôler ALT, AST et bilirubine avant le traitement, toutes les 2 semaines pendant les 3 premiers mois puis chaque mois. Contrôler amylase et lipase au départ et régulièrement. — DailyMed, TABRECTA set_id 455892c3-d144-4ba8-9ab4-79cabff9876d
- Mise en garde majeure · Peut provoquer des réactions d’hypersensibilité graves et une photosensibilité. Suspendre ou arrêter selon la gravité et limiter l’exposition directe aux ultraviolets avec écran solaire et vêtements protecteurs. — DailyMed, TABRECTA set_id 455892c3-d144-4ba8-9ab4-79cabff9876d
Interactions médicamenteuses
- SévèreInducteurs puissants ou modérés du CYP3A
Mécanisme: Ils réduisent l’exposition et peuvent diminuer l’activité antitumorale.
Recommandation: Éviter l’association.
DailyMed, TABRECTA set_id 455892c3-d144-4ba8-9ab4-79cabff9876dhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=455892c3-d144-4ba8-9ab4-79cabff9876d
- ModéréeInhibiteurs puissants du CYP3A
Mécanisme: Ils augmentent l’exposition et peuvent accroître la toxicité.
Recommandation: En cas d’association, surveiller étroitement les effets indésirables.
DailyMed, TABRECTA set_id 455892c3-d144-4ba8-9ab4-79cabff9876dhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=455892c3-d144-4ba8-9ab4-79cabff9876d
- ModéréeSubstrats sensibles du CYP1A2, de la P-gp, de la BCRP, de MATE1 ou MATE2K
Mécanisme: Le capmatinib peut augmenter leur exposition et leur toxicité.
Recommandation: Éviter les substrats à marge thérapeutique étroite ou coordonner une réduction et une surveillance spécifiques.
DailyMed, TABRECTA set_id 455892c3-d144-4ba8-9ab4-79cabff9876dhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=455892c3-d144-4ba8-9ab4-79cabff9876d
Effets indésirables
Communs (≥1%)
œdème · nausées · douleur musculosquelettique · fatigue · vomissements · dyspnée · toux · diminution de l’appétit
Rares mais graves
pancréatite · pneumonite fatale
Grossesse et allaitement
Peut provoquer une toxicité embryofœtale. Vérifier la grossesse avant de commencer. Les femmes et les hommes ayant une partenaire susceptible d’être enceinte doivent utiliser une contraception efficace pendant le traitement et pendant 1 semaine après. Ne pas allaiter pendant le traitement ni pendant 1 semaine après.
Bibliographie récente (PubMed)
Targeted therapies have revolutionized the treatment and improved the outcome for oncogene-driven NSCLC and an increasing number of oncogenic driver therapies have become available. For MET-dysregulated NSCLC (especially MET exon 14 skipping mutations and MET-amplifications, which is one of the most common bypass mechanisms of resistance in oncogene-addicted NSCLC), several anti-MET-targeted therapies have been approved recently (MET exon 14 skipping mutation) and multiple others are in development. In this narrative review, we summarize the role of MET as an oncogenic driver in NSCLC, discuss the different testing methods for exon 14 skipping mutations, gene amplification, and protein overexpression, and review the existing data and ongoing clinical trials regarding targeted therapies in MET-altered NSCLC. As immunotherapy with or without chemotherapy has become the standard of care for advanced NSCLC, immunotherapy data for MET-dysregulated NSCLC are put into perspective. Finally, we discuss future challenges in this rapidly evolving landscape.
The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded. With therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas. Thus, the greatest expectation surrounded the inhibition of the KRAS G12C mutation, which occurs in ∼15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy. Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (N
Alterations in the proto-oncogene MET are associated with tumour development, invasion and metastasis across various solid cancers. Therapeutically actionable MET alterations include MET exon 14 skipping (METex14) mutations, MET amplification and/or MET overexpression and MET fusions, which vary in incidence by tumour type. In contrast to rare de novo MET alterations, acquired MET amplification and/or MET overexpression is a relatively common phenomenon that is associated with distinct clinical implications and responses to treatment. METex14 is a distinct oncogenic driver mutation in non-small-cell lung cancer (NSCLC). To date, the MET tyrosine-kinase inhibitors (TKIs) capmatinib, tepotinib and savolitinib have been approved for the treatment of advanced-stage METex14-mutant NSCLC. However, the treatment paradigms for MET-altered solid tumours are rapidly evolving to include diverse MET-targeted agents. Emerging data support the role of MET TKIs, anti-MET antibodies and MET-directed antibody-drug conjugates (ADCs) as monotherapy or in combination with other therapies for NSCLC or other tumour types with MET amplification and/or overexpression. Indeed, in May 2025, the MET-directed ADC telisotuzumab vedotin was approved by the FDA for patients with previously treated advanced-stage nonsquamous NSCLC overexpressing MET (≥50% of tumour cells with 3+ staining on immunohistochemistry). Understanding the unique MET-related adverse events will be crucial when incorporating these agents into daily clinical practice. In this Review, we highlight the rationale for targeting MET alterations across various solid tumour types and provide a summary of the clinical efficacy and toxicity profiles of the approved and emerging MET-targeted TKIs, monoclonal or bispecific antibodies and ADCs.