Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cancer. 2019 Mar 1;125(5):742-749. doi: 10.1002/cncr.31855. Epub 2018 Dec 3.
The clinical response to anti-programmed cell death 1 (PD-1) antibodies in patients with advanced gastric and gastroesophageal junction (GEJ) cancer in China has not been reported.
This study evaluated the efficacy and safety of SHR-1210, an anti-PD-1 antibody, in patients with advanced gastric/GEJ cancer in a phase 1 trial. The associations between candidate biomarkers (programmed death ligand 1 [PD-L1] expression, mismatch repair status, tumor mutation load, and lactate dehydrogenase [LDH] levels) and the efficacy of SHR-1210 were also explored.
Thirty patients with recurrent or metastatic gastric/GEJ adenocarcinoma who were refractory or intolerant to previous chemotherapy were enrolled between June 2, 2016, and June 8, 2017. Seven patients (23.3%) demonstrated objective responses, including 1 complete response. The objective response rates for patients with PD-L1-positive and PD-L1-negative tumors were 23.1% (3 of 13) and 26.7% (4 of 15), respectively (P = 1.000). Two treatment-related grade 3 or higher adverse events were reported: one was grade 3 pruritus, and the other (3.3%) was grade 5 interstitial lung disease. All 20 patients tested for the mismatch repair status had mismatch repair-proficient tumors, and the response rate was 30.0% (95% confidence interval, 11.9%-54.3%). Patients with a higher mutation load (4 of 10) tended to have better responses than those with fewer mutations (2 of 10), but the difference was not significant (P = .628). Patients with a >10% relative increase from the baseline LDH level were more likely to experience disease progression (90% [9 of 10]) than patients with a ≤10% change (40% [8 of 20]; P = .017).
Anti-PD-1 antibody SHR-1210 shows encouraging efficacy in patients with advanced gastric/GEJ cancer in China, including mismatch repair-proficient subgroups.
在中国，晚期胃癌和胃食管结合部（GEJ）癌患者使用抗程序性细胞死亡蛋白 1（PD-1）抗体的临床反应尚未报道。
本研究在一项 1 期试验中评估了 SHR-1210（一种抗 PD-1 抗体）在晚期胃癌/GEJ 癌患者中的疗效和安全性。还探讨了候选生物标志物（程序性死亡配体 1 [PD-L1]表达、错配修复状态、肿瘤突变负荷和乳酸脱氢酶 [LDH]水平）与 SHR-1210 疗效之间的关系。
2016 年 6 月 2 日至 2017 年 6 月 8 日期间，共纳入 30 例复发或转移性胃/GEJ 腺癌患者，这些患者对先前的化疗不耐受或无效。7 例（23.3%）患者有客观缓解，包括 1 例完全缓解。PD-L1 阳性和 PD-L1 阴性肿瘤患者的客观缓解率分别为 23.1%（13 例中的 3 例）和 26.7%（15 例中的 4 例）（P=1.000）。报告了 2 例与治疗相关的 3 级或更高级别的不良事件：1 例为 3 级瘙痒，另 1 例（3.3%）为 5 级间质性肺病。所有 20 例进行错配修复状态检测的患者均具有错配修复有效的肿瘤，缓解率为 30.0%（95%置信区间，11.9%-54.3%）。10 例中突变负荷较高（4 例）的患者较突变负荷较低（10 例中 2 例）的患者更有可能获得较好的反应，但差异无统计学意义（P=0.628）。与 LDH 水平从基线相对增加≥10%的患者相比，变化≤10%的患者更有可能出现疾病进展（90%[10 例中的 9 例]比 40%[20 例中的 8 例]；P=0.017）。
抗 PD-1 抗体 SHR-1210 在中国晚期胃癌/GEJ 癌患者中显示出令人鼓舞的疗效，包括错配修复有效的亚组。
