ceritinib
Sources réglementaires consultées
Indications approuvées
- Adultes atteints de CBNPC métastatique ALK positif confirmé par test.
Contre-indications
Absolues
- CIMA : hypersensibilité à la substance active ou aux excipients ; l’étiquette FDA n’établit aucune contre-indication formelle.
Mises en garde cliniques
- Surveiller la fonction hépatique au départ, toutes les 2 semaines pendant 3 mois puis mensuellement. Suspendre si PID suspectée et arrêter définitivement si confirmée. — OpenFDA, set_id fff5d805-4ffd-4e8e-8e63-6f129697563e
- Surveiller toxicité gastro-intestinale, QT, bradycardie, glycémie, lipase/amylase et pancréatite. Suspendre si QTc >500 ms sur 2 ECG et arrêter en cas de torsade ou arythmie sévère. — OpenFDA, set_id fff5d805-4ffd-4e8e-8e63-6f129697563e
Interactions médicamenteuses
- SévèreModulateurs du CYP3A et pamplemousse
Mécanisme: Ils peuvent fortement modifier l’exposition au céritinib.
Recommandation: Éviter inducteurs et inhibiteurs puissants et pamplemousse ; si l’inhibiteur est inévitable, appliquer la réduction hépatique indiquée.
OpenFDA, set_id fff5d805-4ffd-4e8e-8e63-6f129697563e
- SévèreSubstrats CYP3A/CYP2C9 étroits, médicaments QT ou bradycardisants
Mécanisme: Peut augmenter l’exposition ou la toxicité cardiaque.
Recommandation: Éviter ou surveiller étroitement.
OpenFDA, set_id fff5d805-4ffd-4e8e-8e63-6f129697563e
Effets indésirables
Communs (≥1%)
diarrhée · nausées · douleur abdominale · vomissements · fatigue
Grossesse et allaitement
Les femmes doivent utiliser une contraception pendant et 6 mois après ; les hommes pendant et 3 mois après. Ne pas allaiter pendant ni 2 semaines après.
Bibliographie récente (PubMed)
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed. A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alec
Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified as potent oncogenic drivers in several malignancies, including non-small cell lung cancer (NSCLC). The discovery of ALK inhibition using a tyrosine kinase inhibitor (TKI) has dramatically improved the outcomes of patients with ALK-mutated NSCLC. However, the emergence of intrinsic and acquired resistance inevitably occurs with ALK TKI use. This review describes the molecular mechanisms of ALK TKI resistance and discusses management strategies to overcome therapeutic resistance.
Background: Soft-tissue sarcoma (STS) is a heterogeneous group of sarcomas with a low incidence. The treatment of advanced disease is poor, and mortality is high. We aimed to generate an overview of the clinical experiences with targeted treatments based on a pre-specified target in patients with STS. Methods: A systematic literature search was conducted in PubMed and Embase databases. The programs ENDNOTE and COVIDENCE were used for data management. The literature was screened to assess the article's eligibility for inclusion. Results: Twenty-eight targeted agents were used to treat 80 patients with advanced STS and a known pre-specified genetic alteration. MDM2 inhibitors were the most-studied drug (n = 19), followed by crizotinib (n = 9), ceritinib (n = 8), and 90Y-OTSA (n = 8). All patients treated with the MDM2 inhibitor achieved a treatment response of stable disease (SD) or better with a treatment duration of 4 to 83 months. For the remaining drugs, a more mixed response was observed. The evidence is low because most studies were case reports or cohort studies, where only a few STS patients were included. Conclusions: Many targeted agents can precisely target specific genetic alterations in advanced STS. The MDM2 inhibitor has shown promising results.
OPINION STATEMENT: Inflammatory myofibroblastic tumor (IMT), characterized by intermediate malignancy and a propensity for recurrence, has presented a formidable clinical challenge in diagnosis and treatment. Its pathological characteristics may resemble other neoplasms or reactive lesions, and the treatment was limited, taking chemotherapies as the only option for those inoperable. However, discovering anaplastic lymphoma kinase (ALK) protein expression in approximately 50% of IMT cases has shed light on a new diagnostic approach and application of targeted therapies. With the previous success of combating ALK+ non-small-cell lung cancers with ALK tyrosine kinase inhibitors (TKIs), crizotinib, a first-generation ALK-TKI, was officially approved by the U.S. Food and Drug Administration in 2020, to treat unresectable ALK+ IMT. After the approval of crizotinib, other ALK-TKIs, such as ceritinib, alectinib, brigatinib, and lorlatinib, have proven their efficacy on ALK+ IMT with sporadic case reports. The sequential treatments of targeted therapies in may provide the insight into the choice of ALK-TKIs in different lines of treatment for unresectable ALK+ IMT.