王妍;刘天舒

• 1:复旦大学附属中山医院肿瘤防治中心，肿瘤内科，上海 200032

摘要(Abstract)：

2021年胃癌药物治疗领域不断取得突破，免疫和靶向治疗取得诸多进展。晚期胃癌一线免疫检查点抑制剂治疗正在不断优化之中，免疫耐药后的治疗和二线后治疗正如火如荼的开展。胃癌辅助治疗和新辅助治疗的免疫检查点抑制剂治疗亦继续往前推进，作为研究也处热烈探讨中。此外，胃癌的新药研发层出不穷，新型药物不断涌现，包括抗体偶联药物、双特异性抗体、新型靶点以及新的治疗方式的联合。新型药物及新型治疗方式的联合都不断为胃癌患者带来新的希望。

关键词(KeyWords)： 胃癌;免疫检查点抑制剂治疗;靶向治疗;抗体偶联药物;双特异性抗体

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 王妍;刘天舒

DOI: 10.13267/j.cnki.syzlzz.2022.018

参考文献(References)：

• [1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
  [2] Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
  [3] Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649):a randomised, open-label, phase 3 trial[J]. Lancet, 2021, 398(10294):27-40.
  [4] Janjigian YY, Ajani JA, Moehler M, et al. LBA7 Nivolumab (NIVO) plus chemotherapy (Chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC):CheckMate 649 study[J]. Ann Oncol, 2021, 32:S1329-S1330.
  [5] National Comprehensive Cancer Network. Gastric Cancer (Version 1.2021)[EB/OL].(2021-02-06)[2022-01-10]. https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf.
  [6] 中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会(CSCO)胃癌诊疗指南2021[M].北京:人民卫生出版社, 2021.
  [7] Xu J, Jiang H, Pan Y, et al. LBA53 Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16):first results of a randomized, double-blind, phase Ⅲ study[J]. Ann Oncol, 2021, 32:S1331.
  [8] Sahin U, TüreciÖ, Manikhas G, et al. FAST:a randomised phase Ⅱ study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma[J]. Ann Oncol, 2021, 32(5):609-619.
  [9] Janjigian YY, Kawazoe A, Yanez PE, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+metastatic gastric or gastroesophageal junction (G/GEJ) cancer:Initial findings of the global phase 3 KEYNOTE-811 study[J]. J Clin Oncol, 2021, 39(15_suppl):4013.
  [10] Catenacci DV, Rosales M, Chung HC, et al. MAHOGANY:margetuximab combination in HER2+unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma[J]. Future Oncol, 2021, 17(10):1155-1164.
  [11] Tintelnot J, Goekkurt E, Binder M, et al. Ipilimumab or FOLFOX with nivolumab and trastuzumab in previously untreated HER2-positive locally advanced or metastatic esophagogastric adenocarcinoma-the randomized phase 2 INTEGA trial (AIO STO 0217)[J]. BMC Cancer, 2020, 20(1):503.
  [12] Xu RH, Zhang YQ, Pan HM, et al. RAINBOW-Asia:a randomized, multicenter, double-blind, phase Ⅲ study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line chemotherapy with platinum and fluoropyrimidine[J]. J Clin Oncol, 2021, 39(3_suppl):199.
  [13] Rha SY, Kim CG, Jung M, et al. Multicenter phase Ⅰb/Ⅱ study of second-line trastuzumab, ramucirumab, and paclitaxel in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (HER-RAM study)[J]. J Clin Oncol, 2021, 39(15_suppl):4063.
  [14] Shitara K, Bang YB, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer[J]. N Engl J Med, 2020, 382(25):2419-2430.
  [15] van Cutsem E, Bartolomeo MD, Smyth E, et al. LBA55 Primary analysis of a phase Ⅱ single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer who progressed on or after a trastuzumab-containing regimen[J]. Ann Oncol, 2021, 32:S1332.
  [16] Peng Z, Liu TS, Wei J, et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase Ⅱ study[J]. Cancer Commun, 2021, 41(11):1173-1182.
  [17] Takiguchi S, Shitara K, Takiguchi N, et al. Neoadjuvant nivolumab monotherapy in patients with resectable gastric cancer:preliminary results from a multicenter study[J]. J Clin Oncol, 2021, 39(15_suppl):4026.
  [18] Liu Y, Han GS, Li HL, et al. Camrelizumab combined with FLOFOX as neoadjuvant therapy for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma:updated results of efficacy and safety[J]. J Clin Oncol, 2021, 39(15_suppl):4036.
  [19] Li S, Yu WB, Xie F, et al. A prospective, phase Ⅱ, single-arm study of neoadjuvant/conversion therapy with camrelizumab, apatinib, S-1±oxaliplatin for locally advanced cT4a/bN+gastric cancer[J]. J Clin Oncol, 2021, 39(15_suppl):4061.
  [20] Li HL, Deng JY, Ge SH, et al. Phase Ⅱ study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma[J]. J Clin Oncol, 2021, 39(15_suppl):4050.
  [21] Li N, Li Z, Fu Q, et al. 160P Phase Ⅱ study of sintilimab combined with FLOT regimen for neoadjuvant treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma[J]. Ann Oncol, 2020, 31:S1302.
  [22] Tang ZQ, Wang Y, Liu D, et al. 1385P Phase Ⅱ study of neoadjuvant camrelizumab combined with chemoradiation for locally advanced proximal gastric cancer (Neo-PLANET, NCT03631615)[J]. Ann Oncol, 2021, 32:S1049.
  [23] Ji J, Shen L, Li Z, et al. AK104(PD-1/CTLA-4 bispecific) combined with chemotherapy as first-line therapy for advanced gastric (G) or gastroesophageal junction (GEJ) cancer:Updated results from a phase Ⅰb study[J]. J Clin Oncol, 2021, 39(3_suppl):232.
  [24] Meric-Bernstam F, Hamilton EP, Beeram M, et al. Zanidatamab (ZW25) in HER2-expressing gastroesophageal adenocarcinoma (GEA):results from a phase Ⅰ study[J]. J Clin Oncol, 2021, 39(3_suppl):164.
  [25] Gong J, Shen L, Luo S, et al. Preliminary efficacy and safety results of KN026 in combination with KN046 in patients with HER2-positive gastrointestinal tumors[C]. Paris:ESMO, 2021.
  [26] Klempner SJ, Bendell JC, Villaflor VM, et al. Safety, efficacy, and biomarker results from a phase Ⅰb study of the anti-DKK1 antibody DKN-01 in combination with pembrolizumab in advanced esophagogastric cancers[J]. Mol Cancer Ther, 2021, 20(11):2240-2249.
  [27] Klempner SJ, Sirard C, Chao J, et al. DKN-01 in combination with tislelizumab and chemotherapy as a first-line therapy in unselected patients with advanced gastroesophageal adenocarcinoma (GEA):DisTinGuish trial[C]. Paris:ESMO, 2021.
  [28] Wainberg ZA, Enzinger PC, Kang YK, et al. Randomized double-blind placebo-controlled phase 2 study of bemarituzumab combined with modified FOLFOX6(mFOLFOX6) in first-line (1L) treatment of advanced gastric/gastroesophageal junction adenocarcinoma (FIGHT)[J]. J Clin Oncol, 2021, 39(3_suppl):160.