Tepotinib (Tepmetko®) was granted accelerated approval in February 2021 for mesenchymalepithelial transition (MET)-altered metastatic non-small cell lung cancer (NSCLC) based on overall response rate and duration. The drug is still under long-term evaluation and healthcare providers should report all serious adverse events that may be associated to FDA’s MedWatch Reporting System.
Targeted therapy; kinase inhibitor
Mechanism of Action
Tepotinib targets MET variants with exon 14 skipping alterations, inhibiting downstream signaling pathways that promote cell division, the ability to grow and survive dislocated from the tumor, and relocation of MET-dependent cancer cells.
Adult patients with metastatic NSCLC with MET exon 14 skipping variants present.
Dosing and Administration
Administer 450 mg orally once a day with food at relatively the same time each day until patients experience intolerable toxicity or disease progression. Do not chew, crush, or split the pills. Take any missed doses until eight hours before the next dose; at which point, skip the missed dose and take the next dose at the regular time.
Common adverse reactions (≥ 20%) were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Grade 3–4 abnormal lab values occurred in ≥ 2% of patients, including decreased lymphocytes, albumin, sodium, and hemoglobin and increased gamma-glutamyltransferase, amylase, ALT, and AST.
Test for the MET biomarker prior to initiating therapy. Confirm pregnancy status in patients of reproductive potential prior to starting therapy. Monitor liver function levels prior to treatment initiation, every two weeks for the first three months, and then once a month or as needed while on treatment. Educate patients on the risk of embryo-fetal toxicity and recommended use of effective contraception during treatment and for one week after the final dose. Monitor patients for pulmonary symptoms indicative of pneumonitis or interstitial lung disease (ILD). Dose modifications are recommended for any-grade pneumonitis or ILD, grade 3 or 4 increased liver enzymes, and any other grade 3 or 4 adverse reaction.
Complete a medication review. Tepotinib is a P-gp inhibitor and should not be administered with P-gp substrates because minimal concentration changes could lead to serious or life-threatening toxicities. Strong CYP3A inhibitors and P-gp inhibitors may increase exposure to tepotinib. Strong CYP3A inducers may reduce tepotinib’s effects.
Teach patients about the side-effect profile and when to notify the healthcare team, including signs and symptoms of worsening respiratory symptoms like trouble breathing, shortness of breath, cough, or fever. Inform patients of frequency of liver function test monitoring. Advise pregnant patients of possible risk to a fetus and recommend that patients or patients’ partners of reproductive potential use contraception during treatment and one week following the last dose. Instruct on proper dosing and administration for oral adherence.
No clinically significant differences were found in safety or effectiveness between younger patients and those aged 65 or older.
Carcinogenicity studies have not been performed. Tepotinib has been found to cause fetal harm.
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