Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non-Small Cell Lung Cancer in the Global Phase III ALEX Study.

Details

Serval ID
serval:BIB_B6BC9B5EAA4E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non-Small Cell Lung Cancer in the Global Phase III ALEX Study.
Journal
Journal of thoracic oncology
Author(s)
Camidge D.R., Dziadziuszko R., Peters S., Mok T., Noe J., Nowicka M., Gadgeel S.M., Cheema P., Pavlakis N., de Marinis F., Cho B.C., Zhang L., Moro-Sibilot D., Liu T., Bordogna W., Balas B., Müller B., Shaw A.T.
ISSN
1556-1380 (Electronic)
ISSN-L
1556-0864
Publication state
Published
Issued date
07/2019
Peer-reviewed
Oui
Volume
14
Number
7
Pages
1233-1243
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
At the prior data cutoff (February 9, 2017) the ALEX trial showed superior investigator-assessed progression-free survival (PFS) for alectinib versus crizotinib in untreated, anaplastic lymphoma kinase (ALK)-positive, advanced NSCLC (hazard ratio = 0.47, 95% confidence interval: 0.34-0.65, p < 0.001). The median PFS in the alectinib arm was not reached versus 11.1 months with crizotinib. Retrospective analyses suggest that the echinoderm microtubule-associated protein-like 4 gene-ALK variant (EML4-ALK) may influence ALK-inhibitor treatment benefit. We present updated analyses, including exploratory subgroup analysis by EML4-ALK variant, after an additional 10 months' follow-up (cutoff December 1, 2017).
Patients were randomized to receive twice-daily alectinib, 600 mg, or crizotinib, 250 mg, until disease progression, toxicity, death, or withdrawal. PFS was determined by the investigators. Baseline plasma and tissue biomarker samples were analyzed by using hybrid-capture, next-generation sequencing to determine EML4-ALK variant.
Baseline characteristics were balanced. Investigator-assessed PFS was prolonged with alectinib (stratified hazard ratio = 0.43, 95% confidence interval: 0.32-0.58). The median PFS times were 34.8 months with alectinib and 10.9 months with crizotinib. EML4-ALK fusions were detectable in 129 patient plasma samples and 124 tissue samples; variants 1, 2, and 3/ab did not affect PFS, objective response rate, or duration of response. Investigator-assessed PFS was longer for alectinib than for crizotinib across EML4-ALK variants 1, 2, and 3a/b in plasma and tissue. Despite longer treatment duration (27.0 months in the case of alectinib versus 10.8 months in the case of crizotinib), the safety of alectinib compared favorably with that of crizotinib.
Alectinib continues to demonstrate superior investigator-assessed PFS versus crizotinib in untreated ALK-positive NSCLC, irrespective of EML4-ALK variant.
Keywords
Adolescent, Adult, Aged, Anaplastic Lymphoma Kinase/genetics, Anaplastic Lymphoma Kinase/metabolism, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Brain Neoplasms/drug therapy, Brain Neoplasms/genetics, Brain Neoplasms/secondary, Carbazoles/administration & dosage, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/pathology, Cohort Studies, Crizotinib/administration & dosage, Female, Follow-Up Studies, Humans, Lung Neoplasms/drug therapy, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Male, Middle Aged, Oncogene Proteins, Fusion/genetics, Piperidines/administration & dosage, Prognosis, Survival Rate, Young Adult, ALEX, Alectinib, EML4-ALK, NGS, Non–small cell lung cancer
Pubmed
Web of science
Open Access
Yes
Create date
15/04/2019 7:27
Last modification date
07/07/2020 5:20
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