1666P - Utility of a novel quantitative EGFR mutated protein analysis using aqua system for EGFR-TKI treatment in non-small cell lung cancer patients

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Diagnostics
Lung and other Thoracic Tumours
Presenter Koichi Goto
Authors K. Goto1, G. Ishii2, K. Fujimoto-Ouchi3, M. Shirane4, H. Ohmatsu5, S. Niho6, K. Yoh6, S. Umemura5, K. Nagai7, Y. Ohe1
  • 1Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2Department Of Pathology, National Cancer Center Hospital East, Kashiwa/JP
  • 3Discovery Pharmacology Department 2, Chugai Pharmaceutical Co., Ltd., 247-8530 - Kanagawa/JP
  • 4Medical Affairs Devision, Chugai Pharmaceuticals Co. Ltd, 1038324 - Tokyo/JP
  • 5Division Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 6National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 7Department Of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa/JP

Abstract

Background

Lung cancer carrying EGFR mutation (muEGFR) expresses good response to EGFR tyrosine kinase inhibitors (TKIs). However, not all patients (pts) with mutation showed similar clinical benefits from EGFR-TKIs. Heterogeneity of tumor cells is considered to be one plausible reason. MuEGFR was usually genotyped in qualitative manner in present clinical practice. In addition, new technology of AQUA system enables us to measure protein levels objectively with considering expression heterogeneity in tissues. Here we investigated the correlation between AQUA score obtained from each specimen and the response and the response duration by EGFR-TKIs.

Methods

Slice sections from genotyped 105 pts with muEGFR and 33 pts with wild-type EGFR were stained by E746-A750 deletion (6B6)- and L858R (43B2)-specific antibodies. Homo- or heterogeneous staining and muEGFR protein levels of these specimens were evaluated with AQUA system.

Results

Concordance rate between genotypes and AQUA-based phenotypes (deletion and L858R), with cut-off values based on ROC curve, were 60% and 82%. Low sensitivity of 6B6 was due to lucking of reactivity for other deletion variants. Alternatively, specificities of both antibodies were 96% and 92%, indicating highly selectivity to muEGFR protein. The AQUA score of 28 pts treated with EGFR-TKIs were varied (5.4 – 798.5) but the falls plot analysis indicated that pts with high AQUA score showed better objective response. Specimens of partial response (PR) had significantly higher AQUA score than those of progression disease (67.4 vs 9.6, p = 0.025). However, there were no differences of AQUA score between specimens of PR and stable disease. When divided pts into two groups based on median AQUA score, the pts with high AQUA score showed a tendency of longer treatment duration (24 mo vs 15 mo, p = 0.210). Especially, the high AQUA score with low intratumoral deviation pts showed longer treatment duration in compared to others. These results indicate that AQUA-based analysis can classify pts carrying genotyped muEGFR into susceptible and less susceptible ones to EGFR-TKIs.

Conclusions

We observed that pts with high AQUA score were more sensitive to EGFR-TKIs. It is important for predicting sensitivity to EGFR-TKIs to examine not only genotyping but also muEGFR protein levels by using AQUA system.

Disclosure

All authors have declared no conflicts of interest.