Jang Jae Yeon, Jeon Youngkyung, Jeong Sun Young, Lim Sung Hee, Kang Won Ki, Lee Jeeyun, Kim Seung Tae
Division of Hematology-Oncology, Department of Internal Medicine, Wonju Severance Christian Hospital, Wonju, Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Gastric Cancer. 2023 Jul;23(3):476-486. doi: 10.5230/jgc.2023.23.e29.
The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC.
Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined.
A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292-39.281) than in the TMB-L (3.31 months; 95% CI, 1.604-5.019; P=0.049).
The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb. When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.
预测晚期胃癌（AGC）对程序性细胞死亡蛋白1（PD-1）检查点抑制剂治疗反应的最佳肿瘤突变负荷（TMB）值仍不清楚。我们旨在研究能够预测PD-1检查点抑制剂在AGC中疗效的最佳TMB临界值。
对2020年10月1日至2021年7月27日期间在韩国三星医疗中心接受帕博利珠单抗或纳武利尤单抗治疗的AGC患者进行回顾性分析。使用二代测序检测法测量TMB水平。基于受试者工作特征曲线分析确定TMB临界值。
共分析了53例患者。预测对PD-1检查点抑制剂的总缓解率（ORR）的TMB临界值定义为每兆碱基13.31个突变（mt/Mb），敏感性为56%，特异性为95%。基于此定义，7例（13.2%）患者为高TMB（TMB-H）。低TMB（TMB-L）组和TMB-H组的ORR不同（8.7%对71.4%，P=0.001）。53例患者的无进展生存期和总生存期（OS）分别为1.93个月（95%置信区间[CI]，1.600-2.268）和4.26个月（95%CI，2.992-5.532）。TMB-H组的中位OS（20.8个月；95%CI，2.292-39.281）长于TMB-L组（3.31个月；95%CI，1.604-5.019；P=0.049）。
在接受PD-1检查点抑制剂单药挽救治疗的AGC患者中，预测治疗反应的TMB临界值为13.31 mt/Mb。当将程序性死亡配体1状态应用于TMB-H时，可以选择可能从PD-1检查点抑制剂中获益的患者。
