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X. Zhang

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-032 - The high protein expression of EGFR using a specific internal domain antibody and loss of PTEN can be used as predictive factors for EGFR TKIs in patients with advanced squamous cell lung cancer (ID 2396)

      09:30 - 16:30  |  Author(s): X. Zhang

      • Abstract

      Over the last decade encouraging new targeting agents have afforded benefits to patients with adenocarcinoma (ie. bevacizumab, erlotinib, gefitinib, crizotinib) but, very few advances were made in the treatment of squamous-cell lung cancer (SqCLC). However, many genomic abnormalities (PTEN, PI3KCA and FGFR1 etc.) are present in SqCLC and there is growing evidence of their cell survival, proliferation, and growth. These expressions have also been related to the resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models. The objective of this study is to investigate the molecular and clinical factors that predict EGFR-TKI efficacy as a second-line or higher therapy in previously treated patients with SqCLC. We especially focused on the protein expression of EGFR, PTEN and PI3KCA gene amplification.

      This retrospective study included 67 SqCLC Korean patients with available tumor tissue and data on EGFR-TKI treatment response and survival. EGFR protein expression in tumor tissue was evaluated by immunohistochemistry (IHC) with a specific antibody that detects the intracellular domain (ID) of EGFR. In addition PTEN expression in tumor tissue was assessed by IHC. PI3KCA gene amplification by quantitative real-time polymerase chain reaction (PCR) and mutational analyses of EGFR exon 19 and 21 by a PCR-based assay were performed.

      The median age was 70 years. The proportions of males and ever smokers were 85% and 82%. Patients had received a median of 2 prior chemotherapy regimens for advanced disease before treatment with EGFR-TKI. Eighty-four percent (n=56) of the patients received erlotinib treatment and the other (n=11) received gefitinib. Of the 54 patients available for response evaluation at 12 weeks, disease control rate was 35% (2 patients in partial response; 17 patients in stable response). The median progression free survival (PFS) and overall survival (OS) were 1.8 and 4.63 months, respectively. Positive EGFR protein expression in tumor tissue was present in 56 patients (85%), loss of PTEN expression (PTEN-negative) in 26 (39%) and PI3KCA gene amplification in 12 (21%). No cases exhibited EGFR activating mutation. But positive EGFR expression correlated with improved PFS (1.87 vs. 0.9 months, p=0.049). Negative PTEN expression was associated with a significantly higher risk of death (3.7 vs. 5.7 months median OS, p=0.028). Multivariable model confirmed that positive EGFR expression correlated with improved PFS (HR = 0.435, 95% CI = 0.21-0.89, p = 0.024) and positive PTEN expression was associated with an increased OS (HR = 0.437, 95% CI = 1.17-4.45, p = 0.015) after adjusting sex, age, performance status and number of previous chemotherapy regimens. The patients with EFGR-negative / PTEN-negative had poorer clinical outcomes than those with positive EGFR or positive PTEN expression: with shorter median PFS (2.1 vs. 4 months, HR = 1.713, p = 0.036). PI3KCA gene amplification was not related to clinical outcomes.

      EGFR and PTEN protein expression could be used to identify which patients with SqCLC are likely to gain a benefit from EGFR-TKIs. The potential clinical application of specific EGFR-ID antibody for prediction of clinical outcomes in SqCLC needs validations.