Abstract LB-306: Pre-treatment sera from NSCLC patients with different outcomes on EGFR-TKI therapy differentially affects sensitivity of lung cancer cell lines to EGFR-TKIs

Abstract

Abstract Background: VeriStrat (VS) is a pre-treatment mass spectrometry-based test that correlates with clinical outcome after 2nd line therapy with gefitinib or erlotinib in advanced NSCLC. The blinded validation showed that patients classified as “Good” had significantly better overall survival than those classified as “Poor” (HR = 0.47 P = 0.0094 in one cohort, HR = 0.33 P = 0.0007 in another).(1) Mass spectra from VS Poor patients have relatively high abundance of eight peaks (proteins) and we believe these reflect an elevated host response to the tumor. Based on our clinical data and our understanding of the VeriStrat signature, we hypothesized that serum from VS Poor patients would increase the resistance of tumor cells to gefitinib in vitro. Methods: The gefitinib sensitive line HCC4006 has an EGFR exon 19 deletion and the resistant line A549 is EGFR wild type. Human sera were from stage IIIB/IV NSCLC patients and characterized as VS Good or Poor. Pools were created by combining sera within each classification and used in growth inhibition assays. Cells were plated (10 replicates/drug concentration; 2,000 cells/well) using two media compositions; RPMI with 10% Good serum or RPMI with 10% Poor serum. After 24 hours, gefitinib was added and the plates were incubated for 6 days. The MTT assay was used to measure growth inhibition. Conclusion: There was a relative decrease in inhibition of sensitive cells when grown in VS Poor serum, but no significant change in resistant tumor cells. We demonstrate that VS Poor serum has a different biological effect on tumor cells than VS Good serum. These results shed light on the nature of the host-tumor interaction and the relative efficacy of targeted therapies in patient populations. We will have similar data from 6–8 additional cell lines with and without EGFR mutations. (1) Taguchi et al. J Natl Cancer Inst. 2007 99(11):838–46. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-306. doi:10.1158/1538-7445.AM2011-LB-306