Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP).

Details

Serval ID
serval:BIB_CF4397F632F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP).
Journal
Journal of thoracic oncology
Author(s)
Dziadziuszko R., Smit E.F., Dafni U., Wolf J., Wasąg B., Biernat W., Finn S.P., Kammler R., Tsourti Z., Rabaglio M., Ruepp B., Roschitzki-Voser H., Stahel R.A., Felip E., Peters S.
ISSN
1556-1380 (Electronic)
ISSN-L
1556-0864
Publication state
Published
Issued date
06/2019
Peer-reviewed
Oui
Volume
14
Number
6
Pages
1086-1094
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Mutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity.
NICHE, a single-arm phase II trial using a two-stage Simon's design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability.
The first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8%) achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95% confidence interval: 6.0-35.4), and median overall survival of 56.0 weeks (95% confidence interval: 16.3- upper limit not estimable). The toxicity profile was in the expected range.
Afatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks.
Keywords
Adult, Afatinib/therapeutic use, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/enzymology, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/pathology, Europe, Female, Humans, Lung Neoplasms/drug therapy, Lung Neoplasms/enzymology, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Male, Middle Aged, Mutation, Prospective Studies, Protein Kinase Inhibitors/pharmacology, Receptor, ErbB-2/genetics, Receptor, ErbB-2/metabolism, Survival Analysis, Afatinib, NSCLC, erb-b2 receptor tyrosine kinase 2 (HER2) mutations
Pubmed
Web of science
Open Access
Yes
Create date
07/04/2019 15:22
Last modification date
25/07/2020 6:19
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