Tepotinib

Tepotinib is an oral targeted anticancer medicine belonging to the class of tyrosine kinase inhibitors. It selectively inhibits the mesenchymal-epithelial transition factor, commonly called MET, which is involved in cellular growth, survival, movement, and tissue repair. In certain cancers, genetic alterations affecting MET, particularly MET exon 14 skipping alterations, can lead to abnormal signalling that supports tumour growth and progression. Tepotinib blocks MET kinase activity and reduces signalling through pathways involved in cancer-cell survival and proliferation. It is primarily used in adults with metastatic non-small cell lung cancer (NSCLC) whose tumours carry the relevant MET alteration. Treatment selection requires molecular testing of tumour tissue or, in appropriate circumstances, a blood-based tumour DNA sample. Tepotinib is administered orally as tablets and is generally taken once daily with food. Unlike conventional chemotherapy, which may affect a wide range of rapidly dividing cells, tepotinib targets a specific molecular pathway, although it can still cause clinically significant adverse effects. These include fluid retention, gastrointestinal symptoms, liver abnormalities, and, less commonly, serious lung inflammation. Treatment requires appropriate patient selection, review of other medicines, and regular clinical and laboratory monitoring. The decision to initiate, continue, adjust, or stop therapy should be made by an oncology specialist according to the patient's clinical condition and applicable prescribing guidance.

Tepotinib was developed as a selective inhibitor of MET receptor tyrosine kinase to target cancers driven by MET pathway alterations. Its clinical development included the VISION trial, a multicentre, open-label study evaluating its activity and safety in patients with advanced or metastatic NSCLC carrying MET exon 14 skipping alterations. The United States Food and Drug Administration (FDA) granted accelerated approval on February 3, 2021, followed by traditional approval on February 15, 2024, after additional efficacy and follow-up data became available. The European Commission granted marketing authorisation in the European Union on February 16, 2022, following assessment by the European Medicines Agency (EMA). These regulatory decisions established tepotinib as a targeted treatment option for appropriately selected adults with MET-altered advanced lung cancer. Approval conditions and treatment eligibility may differ by jurisdiction, so current local prescribing information should be consulted before clinical use.

Tepotinib is indicated for adults with metastatic non-small cell lung cancer harbouring MET exon 14 skipping alterations. The relevant molecular alteration should be confirmed through appropriate tumour molecular testing, with plasma-based testing considered when tumour tissue cannot be obtained, subject to local testing guidance. Tepotinib is used as a single-agent targeted therapy rather than a conventional chemotherapy combination. In the European Union, its authorised indication specifies treatment following prior immunotherapy and/or platinum-based chemotherapy in patients requiring systemic treatment. In the United States, the FDA-approved indication covers adults with metastatic NSCLC carrying the relevant alteration. Its use for other cancers or MET abnormalities should be guided by applicable approvals and specialist assessment rather than assumed from its mechanism of action.

The recommended adult dose in the United States is 450 mg orally once daily with food, generally continued until disease progression or unacceptable toxicity. Tablets should ordinarily be swallowed whole and should not be chewed, crushed, or split. For patients who cannot swallow solid tablets, the approved US prescribing information provides instructions for dispersing the tablets in non-carbonated water; administration through an appropriate nasogastric tube may also be possible under those instructions. If a dose is missed, patients should follow the prescribed instructions and should not take a replacement dose when the next scheduled dose is due within eight hours. If vomiting occurs after a dose, the next dose should be taken at its regular scheduled time. When adverse effects require modification, the dose may be reduced to 225 mg once daily under medical supervision; treatment should be discontinued if this reduced dose cannot be tolerated. Local product information should guide prescribing in other jurisdictions.

Common adverse effects of tepotinib include peripheral oedema, nausea, fatigue, musculoskeletal pain, diarrhoea, shortness of breath, decreased appetite, and rash. Peripheral oedema may cause swelling of the legs, ankles, or other body areas and can affect mobility or daily activities. Laboratory abnormalities may include changes in liver enzymes, pancreatic enzymes, albumin, sodium, haemoglobin, and lymphocyte counts. The severity and combination of side effects vary between patients. Supportive care, symptom assessment, laboratory monitoring, and clinician-directed dose modification may help manage treatment-related problems. Patients should report persistent or worsening symptoms rather than independently changing or stopping their medication.

Important risks associated with tepotinib include interstitial lung disease or pneumonitis, hepatotoxicity, pancreatic toxicity, and embryo-fetal harm. New or worsening cough, breathlessness, or fever may indicate lung inflammation and requires prompt assessment; treatment should be withheld if this complication is suspected and permanently discontinued when confirmed according to applicable prescribing guidance. Liver injury may present with abnormal liver tests, jaundice, dark urine, or abdominal symptoms, and can rarely become severe. Increased amylase or lipase levels and pancreatitis are additional concerns requiring clinical and laboratory evaluation. Pregnancy should be avoided during treatment because tepotinib may harm a developing fetus. There are no formal contraindications listed in the current US prescribing information, but treatment decisions must account for individual risk factors. Depending on the severity of toxicity, clinicians may interrupt treatment, reduce the dose, or permanently discontinue therapy.

Before starting tepotinib, clinicians should confirm the tumour's MET exon 14 skipping status, review medical history and concurrent medicines, and assess liver function and pancreatic enzymes. Liver function tests, including alanine aminotransferase, aspartate aminotransferase, and bilirubin, should be measured before treatment, every two weeks during the first three months, and monthly thereafter or as clinically indicated. Amylase and lipase should also be checked at baseline and regularly during treatment. Pregnancy status and reproductive plans should be reviewed where relevant, with effective contraception advised during treatment and for one week after the final dose. Breastfeeding should be avoided during treatment and for one week after the last dose under US prescribing guidance. Tepotinib can interact with certain medicines transported by P-glycoprotein (P-gp), potentially increasing exposure to those medicines; combinations involving drugs with a narrow therapeutic margin require particular care. All prescription medicines, over-the-counter products, and herbal preparations should be reviewed by the treating clinician or pharmacist.

Confirm MET exon 14 skipping alterations using a validated molecular testing approach before initiating treatment, and document the testing method and result. Review baseline liver function, pancreatic enzymes, respiratory symptoms, body weight, and pre-existing oedema. Explain the importance of taking tepotinib consistently with food and following the locally approved instructions for missed doses and administration difficulties. Patients should be counselled to report new respiratory symptoms, jaundice, persistent abdominal pain, or substantial swelling promptly. Review concomitant medicines for clinically important P-gp interactions and assess the need for closer monitoring when interacting medicines cannot be avoided. Monitor liver enzymes and pancreatic enzymes according to prescribing guidance, and assess oedema and functional status throughout treatment. Dose interruptions or reductions should be based on the severity of toxicity and the applicable product information. Coordinate care between the oncologist, clinical pharmacist, laboratory team, and other healthcare professionals to support safe treatment and timely management of adverse effects.