Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP).
- Dziadziuszko R Medical University of Gdansk, Department of Oncology and Radiotherapy, Gdansk, Poland.
- Smit EF VU University Medical Center, Department of Pulmonary Diseases & Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands.
- Dafni U Frontier Science Foundation-Hellas & National and Kapodistrian University of Athens, Athens, Greece.
- Wolf J University Hospital Cologne, Department of Internal Medicine, Cologne, Germany.
- Wasąg B Medical University of Gdansk, Department of Biology and Genetics, Gdansk, Poland.
- Biernat W Medical University of Gdansk, Department of Pathology, Gdansk, Poland.
- Finn SP Cancer Molecular Diagnostics, St. James's Hospital and Trinity College, Dublin, Ireland.
- Kammler R European Thoracic Oncology Platform (ETOP), Bern, Switzerland.
- Tsourti Z Frontier Science Foundation-Hellas, Athens, Greece.
- Rabaglio M European Thoracic Oncology Platform (ETOP), Bern, Switzerland.
- Ruepp B European Thoracic Oncology Platform (ETOP), Bern, Switzerland.
- Roschitzki-Voser H European Thoracic Oncology Platform (ETOP), Bern, Switzerland.
- Stahel RA University Hospital Zurich, Clinic of Oncology, Zurich, Switzerland.
- Felip E Vall d'Hebron University Hospital, Institute of Oncology, Barcelona, Spain.
- Peters S Centre Hospitalier Universitaire Vaudois (CHUV), Département d'Oncologie, Lausanne, Switzerland. Electronic address: Solange.Peters@chuv.ch.
- 2019-03-03
Published in:
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. - 2019
Afatinib
NSCLC
erb-b2 receptor tyrosine kinase 2 (HER2) mutations
Adult
Afatinib
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung
Europe
Female
Humans
Lung Neoplasms
Male
Middle Aged
Mutation
Prospective Studies
Protein Kinase Inhibitors
Receptor, ErbB-2
Survival Analysis
English
INTRODUCTION
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.jtho.2019.02.017
- PMID 30825613
- Persistent URL
- https://sonar.ch/global/documents/297406
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