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[胃癌有哪些新进展?]

[What's new in gastric cancer?].

作者信息

Masetti Michael, Lorenzen Sylvie

机构信息

Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der TU München, München, Deutschland.

出版信息

Dtsch Med Wochenschr. 2024 Aug;149(17):1015-1020. doi: 10.1055/a-2179-0830. Epub 2024 Aug 15.

DOI:10.1055/a-2179-0830
PMID:39146748
Abstract

In the locally advanced stage, multimodal therapies such as perioperative chemotherapy with FLOT or neoadjuvant radiochemotherapy are recommended. The integration of immunotherapy into these concepts could improve the prognosis. Phase II/III trials such as DANTE, KEYNOTE-585 and MATTERHORN show promising results in terms of pathological remissions but data on survival time extension for unselected patients are so far sobering. Immunotherapies and new targeted therapies offer hope in the palliative treatment of metastatic gastric cancer. Studies such as CheckMate-649 and KEYNOTE-859 show an improvement in survival and response rates. Currently, both pembrolizumab and nivolumab have been approved for the first-line treatment of tumors with positive PD-L1 expression. In HER2-positive tumors, the KEYNOTE-811 study showed that patients benefit from combination therapies with immune checkpoint inhibition and anti-HER2 therapies. The antibody-drug conjugate trastuzumab-deruxtecan is a promising second-line treatment option for HER2-positive tumors after treatment failure with trastuzumab.In addition, the bispecific antibody zanidatamab shows promising results in first-line treatment. New targeted therapies against CLDN18.2 and FGFR2b are showing promising results. The anti-claudin 18.2 (CLDN18.2) antibody zolbetuximab leads to improved survival compared to chemotherapy alone in patients with CLDN18.2 positive disease in first-line therapy, with approval expected in 2024.

摘要

在局部晚期阶段,推荐采用多模式疗法,如使用FLOT进行围手术期化疗或新辅助放化疗。将免疫疗法纳入这些方案可能会改善预后。DANTE、KEYNOTE - 585和MATTERHORN等II/III期试验在病理缓解方面显示出有希望的结果,但迄今为止,关于未选择患者生存时间延长的数据并不乐观。免疫疗法和新的靶向疗法为转移性胃癌的姑息治疗带来了希望。CheckMate - 649和KEYNOTE - 859等研究显示生存率和缓解率有所提高。目前,帕博利珠单抗和纳武利尤单抗均已获批用于一线治疗PD - L1表达阳性的肿瘤。在HER2阳性肿瘤中,KEYNOTE - 811研究表明,患者可从免疫检查点抑制与抗HER2疗法的联合治疗中获益。抗体药物偶联物曲妥珠单抗-德曲妥珠单抗是曲妥珠单抗治疗失败后HER2阳性肿瘤有前景的二线治疗选择。此外,双特异性抗体zanidatamab在一线治疗中显示出有希望的结果。针对CLDN18.2和FGFR2b的新靶向疗法显示出有希望的结果。抗claudin 18.2(CLDN18.2)抗体zolbetuximab在一线治疗CLDN18.2阳性疾病的患者中,与单纯化疗相比可提高生存率,预计2024年获批。

相似文献

1
[What's new in gastric cancer?].[胃癌有哪些新进展?]
Dtsch Med Wochenschr. 2024 Aug;149(17):1015-1020. doi: 10.1055/a-2179-0830. Epub 2024 Aug 15.
2
New developments and standard of care in the management of advanced gastric cancer.晚期胃癌治疗的新进展与护理标准
Clin Res Hepatol Gastroenterol. 2024 Jan;48(1):102245. doi: 10.1016/j.clinre.2023.102245. Epub 2023 Nov 11.
3
The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction.靶向治疗和免疫治疗在晚期转移性和非转移性食管及食管胃交界部癌患者中的疗效。
Updates Surg. 2023 Feb;75(2):313-323. doi: 10.1007/s13304-022-01327-0. Epub 2022 Jul 14.
4
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.zolbetuximab 联合 mFOLFOX6 治疗 Claudin18.2 阳性、HER2 阴性、未经治疗的局部晚期不可切除或转移性胃或胃食管结合部腺癌患者(SPOTLIGHT):一项多中心、随机、双盲、III 期临床试验。
Lancet. 2023 May 20;401(10389):1655-1668. doi: 10.1016/S0140-6736(23)00620-7. Epub 2023 Apr 15.
5
Immunotherapy in Gastric Cancer.胃癌的免疫治疗。
Curr Oncol. 2022 Mar 2;29(3):1559-1574. doi: 10.3390/curroncol29030131.
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Recent progress and current challenges of immunotherapy in advanced/metastatic esophagogastric adenocarcinoma.晚期/转移性食管胃腺癌免疫治疗的最新进展与当前挑战
Eur J Cancer. 2022 Nov;176:13-29. doi: 10.1016/j.ejca.2022.08.023. Epub 2022 Sep 29.
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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).Ipilimumab 或 FOLFOX 联合 Nivolumab 和 Trastuzumab 治疗未经治的 HER2 阳性局部晚期或转移性胃食管腺癌 - 随机 2 期 INTEGA 试验(AIO STO 0217)。
BMC Cancer. 2020 Jun 1;20(1):503. doi: 10.1186/s12885-020-06958-3.
8
Changes in the therapeutic landscape of oesophago-gastric cancers.食管胃结合部癌治疗格局的变化。
Curr Opin Oncol. 2021 Jul 1;33(4):362-367. doi: 10.1097/CCO.0000000000000728.
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FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1.FDA 批准概要:帕博利珠单抗用于表达 PD-L1 的复发性局部晚期或转移性胃或胃食管连接部腺癌。
Oncologist. 2019 Jan;24(1):103-109. doi: 10.1634/theoncologist.2018-0221. Epub 2018 Aug 17.
10
EORTC-1203-GITCG - the "INNOVATION"-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group.EORTC-1203-GITCG - “创新”试验:曲妥珠单抗单药与曲妥珠单抗加帕妥珠单抗联合化疗在 HER2 阳性胃和胃食管交界处腺癌围手术期治疗中的疗效对比:EORTC 胃肠道肿瘤研究组、韩国癌症研究组和荷兰上消化道肿瘤组的一项随机 II 期分组试验。
BMC Cancer. 2019 May 24;19(1):494. doi: 10.1186/s12885-019-5675-4.

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