Activity of Afatinib in Heavily Pretreated Patients With ERBB2 Mutation-Positive Advanced NSCLC: Findings From a Global Named Patient Use Program.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_29FF3A29D783
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Activity of Afatinib in Heavily Pretreated Patients With ERBB2 Mutation-Positive Advanced NSCLC: Findings From a Global Named Patient Use Program.
Journal
Journal of thoracic oncology
Author(s)
Peters S., Curioni-Fontecedro A., Nechushtan H., Shih J.Y., Liao W.Y., Gautschi O., Spataro V., Unk M., Chih-Hsin Yang J., Lorence R.M., Carrière P., Cseh A., Chang G.C.
ISSN
1556-1380 (Electronic)
ISSN-L
1556-0864
Publication state
Published
Issued date
12/2018
Peer-reviewed
Oui
Volume
13
Number
12
Pages
1897-1905
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Approximately 1% to 4% of NSCLC tumors harbor erb-b2 receptor tyrosine kinase 2 (ERBB2) mutation; there is no approved targeted treatment for this subgroup.
Patients with stage IV NSCLC that progressed after clinical benefit on erlotinib/gefitinib and/or had activating EGFR or ERBB2 mutations, had exhausted other treatments, and were ineligible for afatinib trials were enrolled in a named patient use program, receiving afatinib 30 to 50 mg/d on a compassionate basis within routine clinical practice. Efficacy and safety were retrospectively assessed in the subgroup with ERBB2 mutation-positive NSCLC.
Twenty-eight heavily pretreated patients in the named patient use program had a documented ERBB2 mutation by local testing. Median time-to-treatment failure (TTF; time from treatment initiation to discontinuation for any reason) was 2.9 months; eight patients (29%) had TTF greater than 1 year. Objective response rate was 19% (3 of 16 patients with response data achieved partial response) and disease control rate (DCR) was 69% (11 of 16). Among 12 patients for whom type of ERBB2 mutation was specified, 10 had a p.A775_G776insYVMA insertion in exon 20, four of whom (40%) remained on afatinib for more than 1 year. This subgroup had median TTF of 9.6 months, objective response rate of 33% (two of six), and disease control rate of 100% (six of six).
This analysis of patients treated in clinical practice provides further evidence of the activity of afatinib in ERBB2 mutation-positive NSCLC, and suggests that identification of specific subgroups with certain mutations, such as p.A775_G776ins/YVMA insertion in exon 20, could help optimize outcomes with ErbB2-targeted treatment.
Keywords
Adult, Afatinib/therapeutic use, Aged, Aged, 80 and over, Antineoplastic Agents/therapeutic use, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/pathology, Female, Follow-Up Studies, Humans, Lung Neoplasms/drug therapy, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Male, Middle Aged, Mutation, Prognosis, Receptor, ErbB-2/genetics, Retrospective Studies, Salvage Therapy, Afatinib, ERBB2 mutation, NSCLC
Pubmed
Web of science
Open Access
Yes
Create date
20/08/2018 13:33
Last modification date
03/10/2019 5:09
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