Abstract 4405: Tumor mutational burden, as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer

Abstract

Abstract Background: The optimal value of tumor mutational burden (TMB) for predicting treatment response of immunotherapy in advanced gastric cancer (AGC) is still unclear. We aimed to establish the optimal cut-off value of TMB, and evaluate the efficacy of immunotherapy in AGC according to TMB and other markers. Method: From October 1, 2020, to July 27, 2021, at Samsung medical center in Korea, patients with AGC, who received pembrolizumab or nivolumab were included. TMB was measured by next-generation sequencing (NGS)-based assays, and PD-L1 is tested using immune-histochemical assay 22C3 pharmDx. Based on receiver operating characteristic analysis, the cut-point value of TMB was determined as the point where the Youden’s index is maximum. Result: A total of 53 patients were analyzed. The cut-off value of TMB for predicting the overall response of immune checkpoint inhibitors was defined as 13.31 mutations/megabase (mt/mb), with 56% of sensitivity and 95% of specificity. Under this definition of TMB, 7 patients were TMB-high group (≥13.31 mt/mb), while 46 patients were TMB-low group (<13.31 mt/mb). The overall response rate (ORR) had a statistically significant difference between TMB-low (8.7%, n=4/46) and TMB-high patients (71.4%, n=5/7; p=0.001). The progression-free survival (PFS) and overall survival (OS) for 53 patients were 1.93 months (95% CI, 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The OS was longer in the TMB-high group with the median of 20.8 months (95% CI, 2.292-39.281) compared to the TMB-low group with the median of 3.31 months (95% CI, 1.604-5.019; p=0.049). The ORR of the patients whose PD-L1 CPS was 1 or above was not different from the patients whose PD-L1 CPS was lower than 1. Conclusion: In this study, the optimal value of TMB for predicting the objective response rate of immunotherapy in AGC was determined as 13.31 mt/mb. TMB-high (≥13.31 mt/mb) was associated with a better objective response rate, and TMB-high patients exhibited better overall survival. TMB has the potential for predicting therapeutic response to immunotherapy in advanced gastric cancer. Citation Format: Jaeyeon Jang, Youngkyung Jeon, Sun Young Jeong, Ye Ji Jung, Daeho Choi, Joohyun Hong, Jeeyun Lee, Won Ki Kang, Seung Tae Kim. Tumor mutational burden, as a potential predictive marker for the efficacy of immunotherapy in advanced gastric cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4405.