PDF(Pubmed)
Abstract：
UNASSIGNED: Gastric cancer remains one of the deadliest malignancies in the world, thus urgently requiring effective and safe therapeutics. Claudin18.2 is a member of the tight junction protein family specifically expressed in gastric cancer cells. Monoclonal antibodies targeting Claudin18.2 have been receiving increasing attention recently. ASKB589 is a humanized monoclonal antibody targeting Claudin18.2.
UNASSIGNED: This case described a 65-year-old Chinese man diagnosed with gastric cancer metastasizing to the liver and multiple lymph nodes. The biomarker examination revealed that he had proficient mismatch repair (pMMR), human epidermal growth factor receptor 2 (HER2) was negative, and the combined proportion score (CPS) of PD-L1 (22C3) was 1. After being proven to be moderately positive for Claudin18.2 expression, he received ASKB589 and CAPOX (oxaliplatin and capecitabine) chemotherapy. After a six-cycle therapy (from 14 July 2022 to 29 November 2022), the target tumor was evaluated for partial response (PR) by the investigator based on the enhanced CT scan according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. However, this patient also suffered from intolerable ascites that gradually aggravated during the therapy, which was not controlled well by the supporting therapy. Therefore, the patient stopped receiving the combined therapy in our hospital and did not receive any other anti-tumor treatment. After 4 months of discontinuation of the drug, the patient\'s ascites almost disappeared, while the tumor continued to reduce and almost achieved clinically complete relapse (cCR). His progression-free survival (PFS) reached at least 10 months.
UNASSIGNED: This is the first case of severe ascites reported after anti-Claudin18.2 monoclonal antibody treatment for advanced gastric cancer. At the same time, the patient still benefited significantly from this incomplete treatment even after discontinuation of the drug and the PFS reached at least 10 months. The ascites might be an immune adverse effect related to the monoclonal antibody-induced antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Further mechanisms remain to be investigated.
UNASSIGNED: This case described a 65-year-old Chinese man diagnosed with gastric cancer metastasizing to the liver and multiple lymph nodes. The biomarker examination revealed that he had proficient mismatch repair (pMMR), human epidermal growth factor receptor 2 (HER2) was negative, and the combined proportion score (CPS) of PD-L1 (22C3) was 1. After being proven to be moderately positive for Claudin18.2 expression, he received ASKB589 and CAPOX (oxaliplatin and capecitabine) chemotherapy. After a six-cycle therapy (from 14 July 2022 to 29 November 2022), the target tumor was evaluated for partial response (PR) by the investigator based on the enhanced CT scan according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. However, this patient also suffered from intolerable ascites that gradually aggravated during the therapy, which was not controlled well by the supporting therapy. Therefore, the patient stopped receiving the combined therapy in our hospital and did not receive any other anti-tumor treatment. After 4 months of discontinuation of the drug, the patient\'s ascites almost disappeared, while the tumor continued to reduce and almost achieved clinically complete relapse (cCR). His progression-free survival (PFS) reached at least 10 months.
UNASSIGNED: This is the first case of severe ascites reported after anti-Claudin18.2 monoclonal antibody treatment for advanced gastric cancer. At the same time, the patient still benefited significantly from this incomplete treatment even after discontinuation of the drug and the PFS reached at least 10 months. The ascites might be an immune adverse effect related to the monoclonal antibody-induced antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Further mechanisms remain to be investigated.
摘要：
■胃癌仍然是世界上最致命的恶性肿瘤之一，因此迫切需要有效和安全的治疗方法。Claudin18.2是在胃癌细胞中特异性表达的紧密连接蛋白家族的成员。针对Claudin18.2的单克隆抗体最近受到越来越多的关注。ASKB589是一种针对Claudin18.2的人源化单克隆抗体。
■该病例描述了一名65岁的中国男子，被诊断为胃癌转移到肝脏和多个淋巴结。生物标志物检查显示他有熟练的错配修复（pMMR），人表皮生长因子受体2（HER2）为阴性，PD-L1(22C3)合并比例评分(CPS)为1分。在被证明对Claudin18.2表达中等阳性后，患者接受ASKB589和CAPOX(奥沙利铂和卡培他滨)化疗.经过六个周期的治疗（从2022年7月14日至2022年11月29日），研究者根据实体瘤疗效评估标准(RECIST)1.1标准,基于增强CT扫描评估目标肿瘤的部分疗效(PR).然而,该患者还患有无法忍受的腹水，在治疗期间逐渐加重，支持治疗不能很好地控制。因此,患者停止在我院接受联合治疗,未接受任何其他抗肿瘤治疗.停药4个月后，病人的腹水几乎消失了，而肿瘤继续减少并几乎达到临床完全复发（cCR）。他的无进展生存期（PFS）达到至少10个月。
■这是抗Claudin18.2单克隆抗体治疗晚期胃癌后报道的首例严重腹水病例。同时,即使在停药且PFS达到至少10个月后,患者仍可从这种不完全治疗中获益.腹水可能是与单克隆抗体诱导的抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）有关的免疫不良反应。进一步的机制仍有待研究。
■该病例描述了一名65岁的中国男子，被诊断为胃癌转移到肝脏和多个淋巴结。生物标志物检查显示他有熟练的错配修复（pMMR），人表皮生长因子受体2（HER2）为阴性，PD-L1(22C3)合并比例评分(CPS)为1分。在被证明对Claudin18.2表达中等阳性后，患者接受ASKB589和CAPOX(奥沙利铂和卡培他滨)化疗.经过六个周期的治疗（从2022年7月14日至2022年11月29日），研究者根据实体瘤疗效评估标准(RECIST)1.1标准,基于增强CT扫描评估目标肿瘤的部分疗效(PR).然而,该患者还患有无法忍受的腹水，在治疗期间逐渐加重，支持治疗不能很好地控制。因此,患者停止在我院接受联合治疗,未接受任何其他抗肿瘤治疗.停药4个月后，病人的腹水几乎消失了，而肿瘤继续减少并几乎达到临床完全复发（cCR）。他的无进展生存期（PFS）达到至少10个月。
■这是抗Claudin18.2单克隆抗体治疗晚期胃癌后报道的首例严重腹水病例。同时,即使在停药且PFS达到至少10个月后,患者仍可从这种不完全治疗中获益.腹水可能是与单克隆抗体诱导的抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）有关的免疫不良反应。进一步的机制仍有待研究。
