Annals of Oncology Advance Access originally published online on April 6, 2006
Annals of Oncology 2006 17(7):1120-1127; doi:10.1093/annonc/mdl077
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© 2006 European Society for Medical Oncology
Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib
1 University of Colorado Cancer Center, Department of Medicine/Medical Oncology and Pathology, Aurora, CO, USA; 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
* Correspondence to: Dr F. Cappuzzo, Bellaria Hospital, Division of Medical Oncology, Via Altura 3, 40139 Bologna, Italy. Tel: +39-051-6225696; Fax: +39-051-6225057; E-mail: federico.cappuzzo{at}ausl.bo.it
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.
Key words: IGFR-1, PTEN, EGFR, tyrosine kinase inhibitor, gefitinib, non-small-cell lung cancer
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