Afatinib in patients with metastatic or recurrent HER2-mutant lung cancers: a retrospective international multicentre study.
- Lai WV Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Lebas L Toulouse University Hospital, Toulouse, France.
- Barnes TA Princess Margaret Cancer Centre, Toronto, Canada(2); Northern Beaches Cancer Service, Manly NSW Australia(3).
- Milia J Toulouse University Hospital, Toulouse, France.
- Ni A Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Gautschi O Lucerne Cantonal Hospital, Lucerne, Switzerland.
- Peters S Lausanne University Hospital, Lausanne, Switzerland.
- Ferrara R Gustave Roussy, Villejuif, France.
- Plodkowski AJ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Kavanagh J Toronto General Hospital, University Health Network and University of Toronto, Toronto, Canada.
- Sabari JK Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; New York University Langone Health, Laura and Isaac Perlmutter Cancer Center, New York, NY, USA(3).
- Clarke SJ Royal North Shore Hospital, University of Sydney, Sydney, Australia.
- Pavlakis N Royal North Shore Hospital, University of Sydney, Sydney, Australia.
- Drilon A Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Rudin CM Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Arcila ME Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Leighl NB Princess Margaret Cancer Centre, Toronto, Canada(2).
- Shepherd FA Princess Margaret Cancer Centre, Toronto, Canada(2).
- Kris MG Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Mazières J Toulouse University Hospital, Toulouse, France.
- Li BT Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: lib1@mskcc.org.
- 2019-01-28
Published in:
- European journal of cancer (Oxford, England : 1990). - 2019
Afatinib
HER2 mutation
Metastatic lung cancer
Multicentre study
Adenocarcinoma of Lung
Adult
Afatinib
Aged
Aged, 80 and over
Antineoplastic Agents
Female
Follow-Up Studies
Humans
International Agencies
Lung Neoplasms
Male
Middle Aged
Mutation
Neoplasm Recurrence, Local
Prognosis
Receptor, ErbB-2
Retrospective Studies
Survival Rate
English
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.
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1016/j.ejca.2018.11.030
- PMID 30685684
- Persistent URL
- https://folia.unifr.ch/global/documents/24589
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