HER2 insertion YVMA mutant lung cancer: Long natural history and response to afatinib

Bob T Li; Adrian Lee; Sandra O'Toole; Wendy Cooper; Bing Yu; Jamie E Chaft; Maria E Arcila; Mark G Kris; Nick Pavlakis

doi:10.1016/j.lungcan.2015.10.025

HER2 insertion YVMA mutant lung cancer: Long natural history and response to afatinib

Lung Cancer. 2015 Dec;90(3):617-9. doi: 10.1016/j.lungcan.2015.10.025. Epub 2015 Oct 29.

Authors

Bob T Li¹, Adrian Lee², Sandra O'Toole³, Wendy Cooper⁴, Bing Yu⁵, Jamie E Chaft⁶, Maria E Arcila⁷, Mark G Kris⁶, Nick Pavlakis⁸

Affiliations

¹ Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, USA; Sydney Medical School, University of Sydney, Sydney, Australia.
² Sydney Medical School, University of Sydney, Sydney, Australia; Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia.
³ Sydney Medical School, University of Sydney, Sydney, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia.
⁴ Sydney Medical School, University of Sydney, Sydney, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia; School of Medicine, University of Western Sydney, NSW, Australia.
⁵ Sydney Medical School, University of Sydney, Sydney, Australia; Department of Medical Genomics, Royal Prince Alfred Hospital, Sydney, Australia.
⁶ Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, USA.
⁷ Department of Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
⁸ Sydney Medical School, University of Sydney, Sydney, Australia; Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia. Electronic address: nick.pavlakis@sydney.edu.au.

Abstract

Human epidermal growth factor 2 (HER2, ERBB2) mutations in lung cancers are oncogenic drivers that respond to HER2 targeted therapies. Little is known about the sensitivity of subtypes of HER2 mutant lung cancers to targeted agents. We present a patient with HER2 mutant lung cancer with a 12 base pair insertion YVMA (p.A775_G776insYVMA), who had a long natural history and durable partial response to afatinib. We demonstrate that afatinib has activity in patients with HER2 mutant lung cancers with exon 20 YVMA insertions, the most common variant.

Keywords: Afatinib; Human epidermal growth factor receptor 2 (HER2); Lung cancer; Mutation; Targeted therapy.

Publication types

Case Reports
Research Support, N.I.H., Extramural

MeSH terms

Afatinib
Antineoplastic Agents / therapeutic use
Humans
Immunohistochemistry
Lung Neoplasms / diagnosis
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Male
Middle Aged
Mutagenesis, Insertional*
Protein Kinase Inhibitors / therapeutic use
Quinazolines / therapeutic use
Receptor, ErbB-2 / antagonists & inhibitors
Receptor, ErbB-2 / genetics*
Receptor, ErbB-2 / metabolism
Tomography, X-Ray Computed
Treatment Outcome

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Quinazolines
Afatinib
Receptor, ErbB-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding