Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers
| Autor: | Sanne de Haas, Javier de Castro Carpeño, Pilar Garrido, Dariusz M. Kowalski, A. Villegas, Lisa H. Lam, Dolores Isla, Thomas E. Stinchcombe, Christina S. Baik, Rolf A. Stahel, Lukas Bubendorf, Marcello Tiseo, Michael W Lu, Christoph Meyenberg, Achim Rittmeyer, Solange Peters, Philip Bonomi |
|---|---|
| Přispěvatelé: | University of Zurich, Peters, Solange |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Adult Male Cancer Research medicine.medical_specialty Receptor ErbB-2 medicine.medical_treatment Phases of clinical research 610 Medicine & health Kaplan-Meier Estimate Ado-Trastuzumab Emtansine Disease-Free Survival Targeted therapy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Carcinoma Non-Small-Cell Lung medicine Carcinoma Clinical endpoint Biomarkers Tumor Humans 1306 Cancer Research skin and connective tissue diseases Lung cancer neoplasms Aged Neoplasm Staging Aged 80 and over Chemotherapy business.industry Middle Aged medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology chemistry Trastuzumab emtansine 030220 oncology & carcinogenesis 10032 Clinic for Oncology and Hematology Immunohistochemistry 2730 Oncology Female business |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 25(1) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: 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. Patients and Methods: 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. Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|