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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Afatinib in patients with metastatic or recurrent HER2-mutant lung cancers: a retrospective international multicentre
W Victoria Lai1, Louisiane Lebas2, Tristan A Barnes3
1Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Introduction:
HER2 mutations occur in 1-3% of lung adenocarcinomas. With increasing use of next-generation sequencing at diagnosis, more patients with HER2-mutant tumours present for treatment. Few data are available to describe the clinical course and outcomes of these patients when treated with afatinib, a pan-HER inhibitor.
Methods:
We identified patients with metastatic or recurrent HER2-mutant lung adenocarcinomas treated with afatinib among seven institutions across Europe, Australia, and North America between 2009 and 2017. We determined the partial response rate to afatinib, types of HER2 mutations, duration of response, time on treatment, and survival.
Results:
We collected information on 27 patients with stage IV or recurrent HER2-mutant lung adenocarcinomas treated with afatinib. Of 23 patients evaluable for response, three partial responses were noted (13%, 95% confidence interval [CI] 4-33%). In addition, 57% of patients (13/23) had stable disease, and 30% (7/23) had progressive disease. We documented partial responses in patients with HER2 exon 20 insertions, including two with YVMA insertion and one with VAG insertion. Two patients with partial responses were previously treated with trastuzumab and pertuzumab. Median duration of response to afatinib was 6 months (range 5-10); median time on treatment was 3 months (range 1-30) and median overall survival from the date of diagnosis of metastatic or recurrent disease was 23 months (95% CI 18-53 months).
Conclusions:
Afatinib is modestly active in patients with HER2-mutant lung adenocarcinomas, including responses after progression on prior HER2-targeted therapies. However, investigations into the biology of HER2-mutant lung adenocarcinomas and development of better HER2-directed therapies are warranted.
Insights
Afatinib showed modest activity in patients with HER2-mutant lung cancer, including those previously treated with other therapies. Further research into HER2-mutant lung adenocarcinomas and new treatments is needed.
Area of Science:
- Oncology
- Medical Genetics
Background:
- HER2 mutations are found in 1-3% of lung adenocarcinomas.
- Next-generation sequencing is increasing the diagnosis of HER2-mutant lung cancers.
- Limited data exist on the efficacy of afatinib in HER2-mutant lung adenocarcinomas.
Purpose of the Study:
- To evaluate the clinical outcomes of patients with HER2-mutant lung adenocarcinomas treated with afatinib.
- To determine the response rate, duration of response, and survival in this patient population.
Main Methods:
- Retrospective analysis of 27 patients with metastatic or recurrent HER2-mutant lung adenocarcinomas treated with afatinib across seven institutions.
- Data collected included partial response rate, types of HER2 mutations, duration of response, time on treatment, and overall survival.
Main Results:
- A partial response rate of 13% (3/23) was observed in evaluable patients treated with afatinib.
- 57% of patients experienced stable disease, and 30% had progressive disease.
- Responses were noted in patients with HER2 exon 20 insertions, including YVMA and VAG types. Median overall survival was 23 months.
Conclusions:
- Afatinib demonstrates modest activity in HER2-mutant lung adenocarcinomas, including in patients with prior HER2-targeted therapy.
- Further investigation into the biology of HER2-mutant lung adenocarcinomas is warranted.
- Development of novel HER2-directed therapies is crucial for improving patient outcomes.
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