HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients

F. Cappuzzo, L. Toschi, I. Domenichini, S. Bartolini, G. L. Ceresoli, E. Rossi, V. Ludovini, A. Cancellieri, E. Magrini, L. Bemis, W. A. Franklin, L. Crino, P. A. Bunn, F. R. Hirsch, M. Varella-Garcia

Research output: Contribution to journalArticle

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Abstract

In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutations and genomic gain of the epidermal growth factor receptor (EGFR). Preclinical data suggested that HER3 overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2 status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic gain by FISH. Patients with high polysomy and gene amplification were considered as HER3 FISH positive (+). HER3 FISH + pattern was significantly associated with female gender (P = 0.02) and never smoking history (P = 0.02). Patients with HER3+ tumours (26.8%) had a significantly longer time to progression (3.7 vs 2.7, P = 0.04) than patients with HER3-tumours, but not a significantly better response rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response rate (36.4 vs 9.9%, P = 0.03) and time to progression (7.7 vs 2.7 months, P = 0.03) than patients with EGFR- and/or HER3- tumours, but no significantly longer survival. No difference in response was observed according to HER3 status in patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar outcome as patients with HER2- and/or HER3-tumours. Significantly different clinical end points were not observed between patients with HER3+/P-Akt+ and HER3- and/or P-Akt- tumours. Genomic gain for HER3 is not a marker for response or resistance to TKI therapy in advanced NSCLC patients.

Original languageEnglish
Pages (from-to)1334-1340
Number of pages7
JournalBritish Journal of Cancer
Volume93
Issue number12
DOIs
Publication statusPublished - Dec 12 2005

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Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Fluorescence In Situ Hybridization
Neoplasms
Protein-Tyrosine Kinases
gefitinib
Gene Amplification
DNA Sequence Analysis
Survival Rate
Smoking
History
Immunohistochemistry
Mutation
Survival

Keywords

  • EGFR
  • Gefitinib
  • HER3
  • Non-small-cell lung cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cappuzzo, F., Toschi, L., Domenichini, I., Bartolini, S., Ceresoli, G. L., Rossi, E., ... Varella-Garcia, M. (2005). HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients. British Journal of Cancer, 93(12), 1334-1340. https://doi.org/10.1038/sj.bjc.6602865

HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients. / Cappuzzo, F.; Toschi, L.; Domenichini, I.; Bartolini, S.; Ceresoli, G. L.; Rossi, E.; Ludovini, V.; Cancellieri, A.; Magrini, E.; Bemis, L.; Franklin, W. A.; Crino, L.; Bunn, P. A.; Hirsch, F. R.; Varella-Garcia, M.

In: British Journal of Cancer, Vol. 93, No. 12, 12.12.2005, p. 1334-1340.

Research output: Contribution to journalArticle

Cappuzzo, F, Toschi, L, Domenichini, I, Bartolini, S, Ceresoli, GL, Rossi, E, Ludovini, V, Cancellieri, A, Magrini, E, Bemis, L, Franklin, WA, Crino, L, Bunn, PA, Hirsch, FR & Varella-Garcia, M 2005, 'HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients', British Journal of Cancer, vol. 93, no. 12, pp. 1334-1340. https://doi.org/10.1038/sj.bjc.6602865
Cappuzzo, F. ; Toschi, L. ; Domenichini, I. ; Bartolini, S. ; Ceresoli, G. L. ; Rossi, E. ; Ludovini, V. ; Cancellieri, A. ; Magrini, E. ; Bemis, L. ; Franklin, W. A. ; Crino, L. ; Bunn, P. A. ; Hirsch, F. R. ; Varella-Garcia, M. / HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients. In: British Journal of Cancer. 2005 ; Vol. 93, No. 12. pp. 1334-1340.
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abstract = "In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutations and genomic gain of the epidermal growth factor receptor (EGFR). Preclinical data suggested that HER3 overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2 status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic gain by FISH. Patients with high polysomy and gene amplification were considered as HER3 FISH positive (+). HER3 FISH + pattern was significantly associated with female gender (P = 0.02) and never smoking history (P = 0.02). Patients with HER3+ tumours (26.8{\%}) had a significantly longer time to progression (3.7 vs 2.7, P = 0.04) than patients with HER3-tumours, but not a significantly better response rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response rate (36.4 vs 9.9{\%}, P = 0.03) and time to progression (7.7 vs 2.7 months, P = 0.03) than patients with EGFR- and/or HER3- tumours, but no significantly longer survival. No difference in response was observed according to HER3 status in patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar outcome as patients with HER2- and/or HER3-tumours. Significantly different clinical end points were not observed between patients with HER3+/P-Akt+ and HER3- and/or P-Akt- tumours. Genomic gain for HER3 is not a marker for response or resistance to TKI therapy in advanced NSCLC patients.",
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AU - Ceresoli, G. L.

AU - Rossi, E.

AU - Ludovini, V.

AU - Cancellieri, A.

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