ALK inhibitors for ALK-altered paediatric malignancies
Mené dans 10 pays sur 83 enfants ou adolescents (âge ≥12 mois et <18 ans) atteints d'une tumeur ALK+ de stade localement avancé ou métastatique (lymphome anaplasique à grandes cellules, neuroblastome, rhabdomyosarcome, tumeur myofibroblastique inflammatoire), cet essai de phase I évalue la dose maximale tolérée du céritinib et analyse ses caractéristiques pharmacocinétiques (durée médiane de suivi : 33,3 mois)
The phase 1 dose-escalation trial bfy Matthias Fischer and colleagues published in The Lancet Oncology shows high response rates obtained with ceritinib, a second-generation ALK inhibitor,in 83 children with ALK-positive anaplastic large cell lymphoma (ALCL), inflammatory myofibroblastic tumors(IMT), and a subgroup of those with ALK-altered neuroblastomas, confirming and expanding results previously reported withcrizotinib and other ALK inhibitors. The study results showed that ceritinib is tolerable in children, with mild and manageablegastrointestinal and hepatic toxic effects, and a safety profile consistent with thatobserved in adult patients. In the trial by Fischer and colleagues, the recommended dose of ceritinib in children was established as 500 mg/m2 once daily with food, and overall response rates to ceritinib were 75% (95% CI 35–97)in patients with ALCL, 70% (33–93) in those with IMT, and 20% (8–39) in those withneuroblastoma.
The Lancet Oncology , commentaire, 2020