Abstract
Introduction: Several clinical trials showed that EGFR tyrosine kinase inhibitors (TKI) are highly efficacious in patients with non small cell lung cancer (NSCLC) with EGFR mutations. About 80% of tumors with EGFR-activating mutations respond to EGFR TKI. However, there is still 20% of the patients showed primary resistance to EGFR-TKI treatment. Therefore, it is important to identify addition molecular makers predictive of clinical benefit with EGFR TKIs in EGFR-mutated tumors. It is reported that PTEN loss contributes to EGFR-TKI resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. However, there is no report on the efficacy of TKI for patients with cooccurrence of homozygous deletion of PTEN and EGFR mutation. In this study, we investigated the frequency of homozygous loss of PTEN in EGFR-mutant NSCLC tumors in Chinese patients, and evaluated potential relationships between homozygous deletion of PTEN and outcomes for EGFR-mutant NSCLC patients treated with gefitinib.
Methods: 120 patients with stage IIIB and IV NSCLC and harbored EGFR mutation received gefitinib as first-line treatment at the first affiliated hospital of Guangzhou medical university. The Vysis LSI PTEN SpectrumOrange/CEP 10 SpectrumGreen Probes was used to detect losses of the PTEN gene. Database of the 120 patients have been retrospectively analyzed.
Results: Progression-free survival (hazard ratio=2.13, P<0.01) were significantly shorter in patients whose tumors had cooccurrence of homozygous deletion of PTEN and EGFR mutation.
Conclusion: homozygous deletion of PTEN may be useful for identifying EGFR-mutant NSCLC patients unlikely to benefit from treatment with gefitinib.
- Copyright ©ERS 2015