Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers.

Details

Serval ID
serval:BIB_9F5780E6B02C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers.
Journal
Clinical cancer research
Author(s)
Peters S., Stahel R., Bubendorf L., Bonomi P., Villegas A., Kowalski D.M., Baik C.S., Isla D., Carpeno J.C., Garrido P., Rittmeyer A., Tiseo M., Meyenberg C., de Haas S., Lam L.H., Lu M.W., Stinchcombe T.E.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
01/01/2019
Peer-reviewed
Oui
Volume
25
Number
1
Pages
64-72
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
HER2-targeted therapy is not standard of care for HER2-positive non-small cell lung cancer (NSCLC). This phase II study investigated efficacy and safety of the HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with previously treated advanced HER2-overexpressing NSCLC.
Eligible patients had HER2-overexpressing NSCLC (centrally tested IHC) and received previous platinum-based chemotherapy and targeted therapy in the case of EGFR mutation or ALK gene rearrangement. Patients were divided into cohorts based on HER2 IHC (2+, 3+). All patients received T-DM1 3.6 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was investigator-determined overall response rate (ORR) using RECIST v1.1.
Forty-nine patients received T-DM1 (29 IHC 2+, 20 IHC 3+). No treatment responses were observed in the IHC 2+ cohort. Four partial responses were observed in the IHC 3+ cohort (ORR, 20%; 95% confidence interval, 5.7%-43.7%). Clinical benefit rates were 7% and 30% in the IHC 2+ and 3+ cohorts, respectively. Response duration for the responders was 2.9, 7.3, 8.3, and 10.8 months. Median progression-free survival and overall survival were similar between cohorts. Three of 4 responders had HER2 gene amplification. No new safety signals were observed.
T-DM1 showed a signal of activity in patients with HER2-overexpressing (IHC 3+) advanced NSCLC. Additional investigation into HER2 pathway alterations is needed to refine the target population for T-DM1 in NSCLC; however, HER2 IHC as a single parameter was an insufficient predictive biomarker.
Keywords
Ado-Trastuzumab Emtansine/administration & dosage, Ado-Trastuzumab Emtansine/adverse effects, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor/genetics, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/pathology, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic/drug effects, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Receptor, ErbB-2/genetics
Pubmed
Web of science
Create date
19/09/2018 9:34
Last modification date
06/03/2020 6:20
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