Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcSé-crizotinib trial.

Humans Adult Child Adolescent Young Adult Crizotinib / therapeutic use Lymphoma, Large-Cell, Anaplastic / drug therapy Protein-Tyrosine Kinases / therapeutic use Anaplastic Lymphoma Kinase Neoplasm Recurrence, Local / drug therapy Proto-Oncogene Proteins Receptor Protein-Tyrosine Kinases / therapeutic use Protein Kinase Inhibitors / adverse effects Lung Neoplasms / drug therapy

ALK inhibitors Anaplastic large-cell lymphoma ALK(+) Crizotinib

Journal

European journal of cancer (Oxford, England : 1990)

ISSN: 1879-0852

Titre abrégé: Eur J Cancer

Pays: England

ID NLM: 9005373

Informations de publication

Date de publication:
09 2023

Historique:

received: 25 04 2023

revised: 27 06 2023

accepted: 05 07 2023

medline: 29 8 2023

pubmed: 8 8 2023

entrez: 7 8 2023

Statut: ppublish

Résumé

The French phase II AcSé-crizotinib trial aimed to evaluate the safety and efficacy of crizotinib in patients with ALK, ROS1, and MET-driven malignancies, including ALK-positive anaplastic large-cell lymphoma (ALK ALK Twenty-eight patients were enroled between February 2014 and March 2018. Three patients who were not treated were excluded from the analysis. The median age was 19 years. The median previous line of chemotherapy was two. In the 24 patients with an evaluable response, the response rate at 8 weeks was 67% (95% CI: 47-82%). All patients discontinued crizotinib after a median treatment duration of 3.7 months: eight for progression, two for adverse events (AEs) related to prior treatments, and 15 by choice, including six for allogeneic stem-cell transplantation. The median follow-up was 45 months. Nine patients experienced an event: eight relapses (seven after crizotinib discontinuation and one after dose reduction), and one died in complete remission. The median duration of response was 43.3 months (95% CI: 8.3-not reached). The 3-year progression-free and overall survival rates were 40% (95% CI: 23-59%) and 63% (95% CI: 43-79%). Grade 3 or 4 treatment-related AEs occurred in 32% of patients. Crizotinib shows efficacy and an acceptable safety profile in ALK

Sections du résumé

BACKGROUND

METHODS

ALK

RESULTS

Twenty-eight patients were enroled between February 2014 and March 2018. Three patients who were not treated were excluded from the analysis. The median age was 19 years. The median previous line of chemotherapy was two. In the 24 patients with an evaluable response, the response rate at 8 weeks was 67% (95% CI: 47-82%). All patients discontinued crizotinib after a median treatment duration of 3.7 months: eight for progression, two for adverse events (AEs) related to prior treatments, and 15 by choice, including six for allogeneic stem-cell transplantation. The median follow-up was 45 months. Nine patients experienced an event: eight relapses (seven after crizotinib discontinuation and one after dose reduction), and one died in complete remission. The median duration of response was 43.3 months (95% CI: 8.3-not reached). The 3-year progression-free and overall survival rates were 40% (95% CI: 23-59%) and 63% (95% CI: 43-79%). Grade 3 or 4 treatment-related AEs occurred in 32% of patients.

CONCLUSION

Crizotinib shows efficacy and an acceptable safety profile in ALK

Identifiants

DOI: 10.1016/j.ejca.2023.112984 PMID: 37549532

pubmed: 37549532

pii: S0959-8049(23)00336-2

doi: 10.1016/j.ejca.2023.112984

pii:

doi:

Substances chimiques

Crizotinib 53AH36668S

Protein-Tyrosine Kinases EC 2.7.10.1

Anaplastic Lymphoma Kinase EC 2.7.10.1

Proto-Oncogene Proteins 0

Receptor Protein-Tyrosine Kinases EC 2.7.10.1

Protein Kinase Inhibitors 0

Banques de données

ClinicalTrials.gov

['NCT02034981']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

112984

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.