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Annals of Oncology Advance Access published online on April 6, 2006
Annals of Oncology, doi:10.1093/annonc/mdl077
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© 2006 European Society for Medical Oncology
Received October 14, 2005
Revised March 1, 2006
Accepted March 3, 2006

original article

Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib

F. Cappuzzo 1 *, L. Toschi 1, G. Tallini 2, G. L. Ceresoli 3, I. Domenichini 4, S. Bartolini 2, G. Finocchiaro 2, E. Magrini 2, G. Metro 2, A. Cancellieri 2, R. Trisolini 2, L. Crino 2, P. A. Bunn Jr 5, A. Santoro 3, W. A. Franklin 5, M. Varella-Garcia 5, and F. R. Hirsch 5

1 University of Colorado Cancer Center, Department of Medicine/Medical Oncology and Pathology, Aurora, CO, USA; Bellaria-Maggiore Hospital, Department of Medical Oncology, Bologna, Italy
2 Bellaria-Maggiore Hospital, Department of Medical Oncology, Bologna, Italy
3 Istituto Clinico Humanitas, Department of Medical Oncology, Rozzano, Italy
4 CINECA-Interuniversity Consortium, Bologna, Italy
5 University of Colorado Cancer Center, Department of Medicine/Medical Oncology and Pathology, Aurora, CO, USA

* To whom correspondence should be addressed.
F. Cappuzzo, E-mail: federico.cappuzzo{at}ausl.bo.it


  Abstract

Background: The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib.

Patients and methods: One hundred and twenty-four gefitinib-treated patients with advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1 expression by immunohistochemistry.

Results: IGFR-1 was evaluated in 77 patients and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly associated with clinical or biological characteristics. No difference in response to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-. Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3 months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss of PTEN was detected in 19 tumors (20.4%) and was not associated with any clinical or biological characteristic. No difference in terms of response, time to progression and survival was observed between PTEN+ and PTEN- patients. In multivariable analysis IGFR-1 negative status was significantly associated with higher risk of death (hazard ratio 2.21, P = 0.012).

Conclusions: IGFR-1 expression and loss of PTEN are not associated with intrinsic resistance to gefitinib. Clinical relevance of these two biomarkers as determinant for acquired resistance, and the prognostic role of IGFR-1 expression in patients not exposed to TKIs should be evaluated further.

Keywords: IGFR-1; PTEN; EGFR; tyrosine kinase inhibitor; gefitinib; non-small-cell lung cancer.
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