Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
Courses of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Clin Cancer Res. 2020 Jul 15;26(14):3784-3790. doi: 10.1158/1078-0432.CCR-20-0075. Epub 2020 Mar 10.
We evaluated the association between molecular subtypes of advanced gastric cancer (AGC) and the efficacy of standard chemotherapy or immune checkpoint inhibitors.
Patients with AGC who received systemic chemotherapy from October 2015 to July 2018 with available molecular features were analyzed. We investigated the efficacy of standard first- (fluoropyrimidine + platinum ± trastuzumab) and second-line (taxanes ± ramucirumab) chemotherapy, and subsequent anti-PD-1 therapy in patients with four molecular subtypes: MMR-D (mismatch repair deficient), EBV, HER2, and all negative.
410 patients were analyzed: MMR-D 5.9%, EBV 4.1%, HER2 13.7%, and all negative 76.3%. In 285 patients who received standard first-line chemotherapy, the median progression-free survival (PFS) times were 4.2, 6.0, 7.5, and 7.6 months and the objective response rates (ORR) were 31%, 62%, 60%, and 49% in MMR-D, EBV, HER2, and all-negative subtypes, respectively. Multivariate analysis showed shorter PFS in MMR-D versus all-negative patients [HR, 1.97; 95% CIs, 1.09-3.53; = 0.022]. In second-line setting, there were no significant differences in efficacy. In 110 patients who received anti-PD-1 therapy, median PFS times were 13.0, 3.7, 1.6, and 1.9 months and the ORRs were 58%, 33%, 7%, and 13%, respectively. Twelve patients with MMR-D received subsequent anti-PD-1 therapy and showed longer PFS compared with that in 10 (83%) patients who received earlier-line chemotherapy.
MMR-D might result in shorter PFS with first-line chemotherapy for AGC. Subsequent anti-PD-1 therapy achieved higher ORR and longer PFS than prior chemotherapy in most patients with MMR-D, supporting the earlier use of immune checkpoint inhibitors.
我们评估了晚期胃癌（AGC）的分子亚型与标准化疗或免疫检查点抑制剂疗效之间的关系。
分析了 2015 年 10 月至 2018 年 7 月期间接受全身化疗且具有可用分子特征的 AGC 患者。我们研究了四种分子亚型患者的标准一线（氟嘧啶+铂类±曲妥珠单抗）和二线（紫杉类±雷莫芦单抗）化疗以及随后的抗 PD-1 治疗的疗效：错配修复缺陷（MMR-D）、EBV、HER2 和均为阴性。
共分析了 410 例患者：MMR-D 占 5.9%，EBV 占 4.1%，HER2 占 13.7%，均为阴性占 76.3%。在 285 例接受标准一线化疗的患者中，MMR-D、EBV、HER2 和均为阴性患者的中位无进展生存期（PFS）分别为 4.2、6.0、7.5 和 7.6 个月，客观缓解率（ORR）分别为 31%、62%、60%和 49%。多变量分析显示，与均为阴性患者相比，MMR-D 患者的 PFS 更短[风险比（HR），1.97；95%置信区间（CI），1.09-3.53； = 0.022]。二线治疗时，疗效无显著差异。在 110 例接受抗 PD-1 治疗的患者中，中位 PFS 分别为 13.0、3.7、1.6 和 1.9 个月，ORR 分别为 58%、33%、7%和 13%。12 例 MMR-D 患者接受了后续抗 PD-1 治疗，与 10 例（83%）接受更早线化疗的患者相比，PFS 更长。
MMR-D 可能导致 AGC 一线化疗的 PFS 更短。在大多数 MMR-D 患者中，与先前的化疗相比，后续抗 PD-1 治疗的 ORR 和 PFS 更高，支持更早使用免疫检查点抑制剂。
