lenvatinib
Sources réglementaires consultées
Indications approuvées
- Chez l’adulte, cancer différencié de la thyroïde progressif, localement avancé ou métastatique, résistant à l’iode radioactif ; carcinome hépatocellulaire avancé ou non résécable sans traitement systémique antérieur ; et cancer de l’endomètre avancé ou récidivant progressant pendant ou après un traitement au platine et non éligible à une chirurgie ou radiothérapie curative, en association au pembrolizumab.
- Profil États-Unis : carcinome rénal avancé en première ligne avec pembrolizumab ou après un traitement antiangiogénique avec évérolimus ; cancer de l’endomètre avancé pMMR ou non MSI-H après progression sous traitement systémique et sans option curative, avec pembrolizumab.
Contre-indications
Absolues
- Profil CIMA : hypersensibilité au lenvatinib ou à ses excipients.
- Profil CIMA : allaitement.
Mises en garde cliniques
- Mise en garde majeure · Contrôler et traiter l’hypertension avant et pendant le traitement. Surveiller dysfonction cardiaque, thrombose artérielle, hépatotoxicité, insuffisance rénale, protéinurie, diarrhée, perforation ou fistule gastro-intestinale, hémorragie, dysfonction thyroïdienne et encéphalopathie postérieure réversible ; suspendre, réduire ou arrêter selon la gravité. — DailyMed, LENVIMA set_id f4bedd21-efde-44c6-9d9c-b48b78d7ed1e
- Mise en garde majeure · Peut prolonger le QT. Corriger les troubles électrolytiques, contrôler le calcium au moins chaque mois et surveiller l’ECG en cas de risque ; suspendre si le QT dépasse 500 ms ou augmente d’au moins 60 ms par rapport à la valeur initiale. — DailyMed, LENVIMA set_id f4bedd21-efde-44c6-9d9c-b48b78d7ed1e
- Mise en garde majeure · Peut altérer la cicatrisation et provoquer une ostéonécrose de la mâchoire. Suspendre au moins 1 semaine avant une chirurgie programmée et ne reprendre qu’au moins 2 semaines après une chirurgie majeure et après cicatrisation adéquate ; réaliser une évaluation dentaire préventive si nécessaire. — DailyMed, LENVIMA set_id f4bedd21-efde-44c6-9d9c-b48b78d7ed1e
Interactions médicamenteuses
- SévèreMédicaments prolongeant le QT
Mécanisme: Ils peuvent augmenter le risque de prolongation du QT et d’arythmie.
Recommandation: Éviter l’association si possible ; si elle est nécessaire, corriger les électrolytes et renforcer la surveillance ECG.
DailyMed, LENVIMA set_id f4bedd21-efde-44c6-9d9c-b48b78d7ed1ehttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4bedd21-efde-44c6-9d9c-b48b78d7ed1e
Effets indésirables
Communs (≥1%)
hypertension · diarrhée · diminution de l’appétit · perte de poids · fatigue · nausées · protéinurie · stomatite · vomissements · syndrome main-pied
Grossesse et allaitement
Peut nuire au fœtus. Vérifier la grossesse avant de commencer et utiliser une contraception efficace pendant le traitement et pendant au moins 30 jours après ; si une contraception hormonale orale est utilisée, ajouter une méthode barrière. L’allaitement est contre-indiqué dans le profil CIMA ; le profil FDA recommande de ne pas allaiter pendant le traitement ni pendant 1 semaine après. La fertilité peut être altérée.
Bibliographie récente (PubMed)
Approximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer. Papillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma. Approximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival
Patients with unresectable hepatocellular carcinoma have a poor prognosis, and treatments with long-term benefits are needed. We report results from the preplanned interim analysis of the CheckMate 9DW trial assessing nivolumab plus ipilimumab versus lenvatinib or sorafenib for unresectable hepatocellular carcinoma in the first-line setting. This open-label, randomised, phase 3 trial enrolled patients aged 18 years or older with unresectable hepatocellular carcinoma without previous systemic therapy at 163 hospitals and cancer centres across 25 countries in Asia, Australia, Europe, North America, and South America. Patients had at least one measurable untreated lesion per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, a Child-Pugh score of 5 or 6, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) via an interactive response technology system to receive nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) intravenously every 3 weeks for up to four doses, followed by nivolumab 480 mg every 4 weeks or investigator's choice of either oral lenvatinib (8 mg or 12 mg mg daily depending on bodyweight) or oral sorafenib (400 mg twice daily). Randomisation was stratified by aetiology; the presence of macrovascular invasion, extrahepatic spread, or both; and baseline alpha-fetoprotein concentration. The primary endpoint was overall survival, which was assessed in all randomly assigned patients; safety was an exploratory endpoint and was assessed in all randomly assigned patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04039607 (ongoing). Between Jan 6, 2020, and Nov 8, 2021, 668 patients were randomly assigned to nivolumab plus ipilimumab (n=335) or lenvatinib or sorafenib (n=333). Early crossing of the overall survival Kaplan-Meier curves reflected a higher number of deaths during the first 6 months after randomisation with nivolumab plus
Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed. A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who rece
Thyroid cancer (TC) invariably remains the most prevalent endocrine cancer in the world. Major histological forms of TC include papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid carcinoma (ATC), each of which has a unique clinical and molecular profile. The incidence rate of TC is higher in females, and unfortunately, it has tended to increase over the last several years. Yet the treatment of advanced or aggressive TC forms has improved recently because of developments in immunotherapy and targeted medicines, including PD-1 inhibitors and tyrosine kinase inhibitors (e.g., lenvatinib, sorafenib). Imaging, fine-needle aspiration biopsies, and molecular testing are implemented in the diagnostic process, e.g., in search of mutations that might affect prognosis and provide the most successful treatment option. Chemotherapy, immunotherapy, radioactive iodine therapy (RAI), surgery (such as a total thyroidectomy), and molecularly targeted therapies are currently standard treatment modalities in TC. Optimizing patient outcomes requires better diagnostic precision and individualized treatment regimens based on the genetic profile and tumor subtype. To improve survival and quality of life, it is critical to comprehend the complex etiology of TC and the changing therapeutic landscape.
Hepatocellular carcinoma (HCC) is one of the most common solid malignancies worldwide. A large proportion of patients with HCC are diagnosed at advanced stages and are only amenable to systemic therapies. We have witnessed the evolution of systemic therapies from single-agent targeted therapy (sorafenib and lenvatinib) to the combination of a checkpoint inhibitor plus targeted therapy (atezolizumab plus bevacizumab therapy). Despite remarkable advances, only a small subset of patients can obtain durable clinical benefit, and therefore substantial therapeutic challenges remain. In the past few years, emerging systemic therapies, including new molecular-targeted monotherapies (for example, donafenib), new immuno-oncology monotherapies (for example, durvalumab) and new combination therapies (for example, durvalumab plus tremelimumab), have shown encouraging results in clinical trials. In addition, many novel therapeutic approaches with the potential to offer improved treatment effects in patients with advanced HCC, such as sequential combination targeted therapy and next-generation adoptive cell therapy, have also been proposed and developed. In this Review, we summarize the latest clinical advances in the treatment of advanced HCC and discuss future perspectives that might inform the development of more effective therapeutics for advanced HCC.