Abstract 5543: Low ATM expression is associated with improved progression-free and overall survival in advanced gastric cancer patients treated with platinum-based chemotherapy

Abstract

Abstract Introduction: Platinum-based combination chemotherapy regimens represent standard approaches for locally advanced and metastatic gastric adenocarcinoma. Ataxia-teleangiectasia mutated protein (ATM) plays a critical role in repairing DNA damage to double-stand breaks. Tumors deficient in ATM (defined as pathologic loss measured by IHC) are hypothesized to demonstrate increased susceptibility platinum chemotherapy. Methods: We retrospectively reviewed patients from a single center (Samsung Medical Center, Seoul, South Korea) with advanced, unresectable gastric cancer (stage 3b or higher) receiving capecitabine/oxaliplatin (XELOX) from 2013-2017. Clinicopathologic data, treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed according to level of ATM expression by immunohistochemistry (IHC). Low-expression of ATM was defined as greater than 50% loss by IHC. Two-tailed, unpaired t-tests and Fisher's exact tests were used to compare outcomes between patients with preserved ATM versus low ATM expression. Kaplan-Meier survival analysis was used to compare disease-free survival and overall survival; the log-rank test was used to determine statistical significance. Results: During the study period, 138 patients underwent treatment with XELOX for a diagnosis of advanced gastric cancer. Median (IQR) follow-up time was 11.8 mo. (6.8-17.3). Between patients with ATMintact or ATMlow, there were no significant differences in mean age, sex, final pathologic diagnosis, or mean number of cycles of chemotherapy received. Kaplan-Meier analysis demonstrated that patients with ATM low were associated with a longer PFS (ATMlow 14.9 mo versus ATMintact 6.8 mo.) (HR 0.24, [0.18-0.34, 95% CI], p<0.0001), and longer OS (ATMlow 30.0 mo. versus ATMintact 14.7) (HR 0.23, [0.17-0.33, 95% CI], p<0.0001). There was no difference in response rates between the two groups. Conclusions: This retrospective, case-control study in patients with advanced gastric cancer shows improved survival in patients with ATMlow tumors compared with ATMintact tumors after treatment with platinum-based chemotherapy. Findings are suggestive and require prospective validation in cohorts of patients with ATMlow/ATMintact tumors. Citation Format: Munveer S. Bhangoo, Hubert Y. Luu, Seung Tae Kim, Jeeyun Lee, Joseph Chao, Samuel J. Klempner. Low ATM expression is associated with improved progression-free and overall survival in advanced gastric cancer patients treated with platinum-based chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5543.