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Lung Cancer. 2016 Sep;99:53-6. doi: 10.1016/j.lungcan.2016.05.030. Epub 2016 May 31.

Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers.

Author information

1
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, NY, USA. Electronic address: engj@mskcc.org.
2
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, NY, USA.
4
Department of Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
5
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, NY, USA; Sydney Medical School, University of Sydney, Sydney, Australia.

Abstract

Human epidermal growth factor receptor 2 (HER2, ERBB2) mutations occur in 3% of lung adenocarcinomas. While case reports and series have shown activity of HER2 targeted agents in these patients, little is known about outcomes of chemotherapies. Patients with stage IV HER2-mutant lung cancers at Memorial Sloan Kettering were reviewed. Patient demographics, types of HER2 mutations, duration of systemic treatments and survival were analyzed. We identified 38 patients with HER2-mutant lung cancers: median age 62; majority were women (n=24), never smokers (n=22), and all had adenocarcinomas. A 12 base pair in-frame insertion YVMA in exon 20 (p.A775_G776insYVMA) was present in 24 (63%, 95% CI 46-78%) patients. In addition, there were four 9 base pair insertions, one 6 base pair insertion, and five 3 base pair insertions in exon 20, and four single bp substitutions (exon 20 L755F, V777L, D769H, exon 8 S310F). The median overall survival from date of diagnosis of stage IV disease was 2.3 years (95% CI 1.2-2.6). The median duration of chemotherapy was 4.3 months (68 treatments, range 0-21 months): 6.2 months for pemetrexed ┬▒platinum/bevacizumab, 4 months for taxane ┬▒platinum/bevacizumab, 2.6 months for gemcitabine, 3.5 months for vinorelbine. The median duration of HER2 tyrosine kinase inhibitors was 2.2 months (28 treatments, range 0.3-16.3 months). As we search for better targeted therapies for patients with HER2-mutant lung cancers, chemotherapy remains an important component of care.

KEYWORDS:

Chemotherapy; Human epidermal growth factor receptor 2 (HER2); Lung cancer; Mutation; Targeted therapy

PMID:
27565914
PMCID:
PMC5305295
DOI:
10.1016/j.lungcan.2016.05.030
[Indexed for MEDLINE]
Free PMC Article

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