Mas Léo, Bachet Jean-Baptiste
Hôpital Pitié Salpêtrière, AP-HP, service d'hépato-gastroentérologie et oncologie digestive, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
Hôpital Pitié Salpêtrière, AP-HP, service d'hépato-gastroentérologie et oncologie digestive, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
Bull Cancer. 2022 Oct;109(10):1082-1087. doi: 10.1016/j.bulcan.2022.06.009. Epub 2022 Aug 4.
Gastrointestinal stromal tumors (GIST) are rare digestive tumors. Activating KIT mutations are the most common molecular alteration in these patients, identified in approximately 70 % of cases, followed by PDGFRA mutations (10-15 %), of which the D842V mutation accounts for most cases. Succinate dehydrogenase (SDH) deficiency and alterations involving NF1, BRAF, RAS or NTRK genes are rare molecular subgroups. In advanced GIST, treatment is based on tyrosine kinase inhibitors, including imatinib, which has been the standard first-line treatment since the early 2000s, with sunitinib and regorafenib as second- and third-line standards, respectively. Two new compounds have recently been evaluated in patients with advanced GIST. Ripretinib has become the validated fourth-line therapy for patients with KIT or PDGFRA non-D842V mutations, and avapritinib has been shown to be effective in patients with D842V mutations who were previously resistant to validated treatments. Avapritinib is now the recommended first-line treatment in this subgroup and may represent an additional option, whose place remains to be clarified, in pre-treated patients without D842V mutations. Specific treatments are available or under evaluation for some rare subgroups, and new therapeutic strategies are likely to further improve the management of advanced GIST in the coming years. This overview summarizes the results of recent trials and the place of these new molecules, as well as the main strategies under development for advanced GIST.
胃肠道间质瘤（GIST）是罕见的消化道肿瘤。激活型KIT突变是这些患者中最常见的分子改变，约70%的病例可检测到，其次是PDGFRA突变（10%-15%），其中D842V突变占大多数病例。琥珀酸脱氢酶（SDH）缺陷以及涉及NF1、BRAF、RAS或NTRK基因的改变是罕见的分子亚组。在晚期GIST中，治疗基于酪氨酸激酶抑制剂，包括伊马替尼，自21世纪初以来它一直是标准的一线治疗药物，舒尼替尼和瑞戈非尼分别作为二线和三线标准治疗药物。最近有两种新化合物在晚期GIST患者中进行了评估。瑞派替尼已成为KIT或PDGFRA非D842V突变患者的经证实的四线治疗药物，阿伐替尼已被证明对先前对经证实的治疗耐药的D842V突变患者有效。阿伐替尼现在是该亚组推荐的一线治疗药物，对于无D842V突变的经治患者可能是一个有待明确地位的额外选择。对于一些罕见亚组有特定治疗方法可用或正在评估中，未来几年新的治疗策略可能会进一步改善晚期GIST的管理。本综述总结了近期试验结果、这些新分子的地位以及晚期GIST正在开发的主要策略。
