Introduction: Around 10-30% of patients with EGFR-mutation positive lung adenocarcinoma do not have objective response to EGFR-TKI, whilst the majority of the EGFR-mutation positive patients eventually develop acquired resistance. We have recently demonstrated that the distinct S100A9+ myeloid derived suppressor cells (MDSC) predicted poor outcome in response to cisplatin-based chemotherapy in patients with advanced NSCLC. In this study, we tested whether numbers of circulating S100A9+ MDSC, among other potential factors, could be a predictor for treatment response to EGFR-TKI.

Methods: Between 2010-2012, thirty-four patients with pathologically proved, stage IIIB-IV lung adenocarcinoma with sensitizing EGFR-mutations, were prospectively enrolled. Gefitinib was used as the first line treatment. Pretreatment S100A9 MDSC was determined by FACS analysis and serum HGF by ELISA.

Results:

Among the patients, 47.1% (16/34) had Ex19Del and 50.0% (17/34) had L858R mutations. The objective response rate was 84.4% and the median progression-free survival (PFS) 10.16 months (95% CI 8.18-12.14 months). In univariate analysis, body weight loss, brain metastasis and S100A9 MDSC (p = 0.008, 0.022 and 0.014, respectively), but not gender, smoking, type of EGFR mutation, or serum HGF, were significant factors for PFS. Multivariate Cox regression analysis revealed brain metastasis (HR=3.924, 95% CI 1.449-10.627, p=0.007) and S100A9+ MDSC (HR=4.944, 95% CI 1.578-15.490, p=0.006) were both independent factors for PFS. When the medium number of S100A9 MDSC, e.g. 17.9% of the PBMC, was chosen as a cut off level, patients with high MDSC had shorter PFS compared with those with low MDSC (median 7.2 months (95% CI, 5.5-8.9 months) vs. 12.7 months (95% CI, 8.1-17.2 months), respectively, p=0.014 by Log-Rank Test).

Conclusions: Pretreatment S100A9+ MDSC and brain metastasis are independent predictors for shorter PFS to EGFR TKI in EGFR-mutation positive patients. This MDSC might potentially play some roles in treatment response to EGFR-TKI.

Keyword: NSCLC, S100A9+ MDSC, EGFR mutation, EGFR-TKI

Citation Format: Po-Hao Feng, Chih-Teng Yu, Kang-Yun Lee. Circulating s100a9 myeloid-derived suppressor cells are predictive for poor pfs in patients with egfr mutation positive lung adenocarcinoma treated with gefitinib. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2543. doi:10.1158/1538-7445.AM2014-2543