Depotte Léonard, Palle Juliette, Rasola Cosimo, Broudin Chloé, Afrăsânie Vlad-Adrian, Mariani Antoine, Zaanan Aziz
Department of Digestive Oncology, Georges Pompidou European Hospital, Assistance Publique - Hôpitaux de Paris, University of Paris Cité, France.
Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Clin Res Hepatol Gastroenterol. 2024 Jan;48(1):102245. doi: 10.1016/j.clinre.2023.102245. Epub 2023 Nov 11.
Advanced gastric adenocarcinoma is a common disease with a poor prognosis whose treatment has for decades been based on cytotoxic chemotherapy, including platinum salts in first-line, and taxane or irinotecan in second or later line. Recent years have seen the emergence of new drugs that have improved patient survival, such as trastuzumab in first-line for HER2-positive tumors, ramucirumab alone or in combination with paclitaxel in second-line, and trifluridine-tipiracil beyond the second-line treatment. More recently, two monoclonal antibodies have demonstrated their efficacy in combination with oxaliplatin-based first-line chemotherapy, nivolumab (anti-PD1) for PD-L1 CPS ≥5 tumors, and zolbetuximab for tumors overexpressing Claudin 18.2. In addition, regorafenib has been also showed effective in phase 3 trial for heavily pretreated patients. Based on phase 2 studies, trastuzumab-deruxtecan was approved in 2022 by the EMA for HER2-positive pretreated patients. This agent is currently evaluated in phase 3 study (DESTINY-Gastric04 trial), as are several other anti-HER2 (zanidatamab, margetuximab, tucatinib), immune checkpoint inhibitors, or targeted therapies (anti-FGFR2b).
晚期胃腺癌是一种常见疾病，预后较差，几十年来其治疗一直基于细胞毒性化疗，一线治疗包括铂盐，二线及后续治疗包括紫杉烷或伊立替康。近年来出现了一些改善患者生存率的新药，如一线治疗HER2阳性肿瘤的曲妥珠单抗、二线治疗中单独使用或与紫杉醇联合使用的雷莫西尤单抗，以及二线以上治疗的曲氟尿苷-替匹嘧啶。最近，两种单克隆抗体已证明与基于奥沙利铂的一线化疗联合使用有效，即PD-L1 CPS≥5肿瘤使用纳武利尤单抗（抗PD1），Claudin 18.2过表达肿瘤使用zolbetuximab。此外，瑞戈非尼在针对经过大量预处理患者的3期试验中也显示出有效性。基于2期研究，曲妥珠单抗-德曲妥珠单抗于2022年被欧洲药品管理局批准用于HER2阳性的预处理患者。该药物目前正在3期研究（DESTINY-Gastric04试验）中进行评估，其他几种抗HER2药物（zanidatamab、margetuximab、图卡替尼）、免疫检查点抑制剂或靶向疗法（抗FGFR2b）也是如此。
