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Eur J Cancer. 2019 Mar;109:28-35. doi: 10.1016/j.ejca.2018.11.030. Epub 2019 Jan 24.

Afatinib in patients with metastatic or recurrent HER2-mutant lung cancers: a retrospective international multicentre study.

Author information

1
Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2
Toulouse University Hospital, Toulouse, France.
3
Princess Margaret Cancer Centre, Toronto, Canada(2); Northern Beaches Cancer Service, Manly NSW Australia(3).
4
Lucerne Cantonal Hospital, Lucerne, Switzerland.
5
Lausanne University Hospital, Lausanne, Switzerland.
6
Gustave Roussy, Villejuif, France.
7
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
8
Toronto General Hospital, University Health Network and University of Toronto, Toronto, Canada.
9
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).
10
Royal North Shore Hospital, University of Sydney, Sydney, Australia.
11
Princess Margaret Cancer Centre, Toronto, Canada(2).
12
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.

Abstract

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.

KEYWORDS:

Afatinib; HER2 mutation; Metastatic lung cancer; Multicentre study

PMID:
30685684
PMCID:
PMC6426688
[Available on 2020-03-01]
DOI:
10.1016/j.ejca.2018.11.030

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