Background:Zolbetuximab, a monoclonal antibody targeting claudin-18.2 (CLDN18.2), which was recently approved as first-line treatment for advanced gastric cancer (AGC), presents unique safety challenges, particularly infusion-related gastrointestinal toxicity and hypoalbuminemia. This study aimed to present our experience with zolbetuximab administration in patients with AGC, focusing on the safety and management effectiveness of our adapted protocol in routine clinical practice.Methods:This study presents our single-institution real-world experience implementing a proactive management protocol (“Project VYLOY”) using zolbetuximab to mitigate these toxicities. We adopted a standardized stepwise infusion protocol and antiemetic premedication to reduce infusion-related nausea and vomiting. Patients with CLDN18.2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received zolbetuximab combined with chemotherapy were included.Results:Twenty-four patients were included. The median infusion duration was 215 min, with an interruption rate of 25.0%. In cycle 1, 62.5% experienced infusion-associated adverse events, primarily grade 1 nausea (54%) and vomiting (25%). Hypoalbuminemia (grade ≥ 2) occurred in 57% of first-line patients, potentially linked to zolbetuximab-induced gastritis and gastrointestinal protein loss. Proactive antiemetic support and infusion rate adjustments substantially reduced infusion interruptions in subsequent cycles (10.9%). Patients without prior gastrectomy had higher nausea and vomiting rates, confirming the stomach’s role in mediating toxicity.Conclusions:Our results suggest that proactive management can improve the safety and tolerability of zolbetuximab, especially by reducing infusion-related toxicity in real-world practice.
背景：佐贝妥昔单抗是一种靶向claudin-18.2（CLDN18.2）的单克隆抗体，近期获批作为晚期胃癌的一线治疗药物，其安全性面临独特挑战，尤其是输注相关胃肠道毒性和低白蛋白血症。本研究旨在分享我们在晚期胃癌患者中应用佐贝妥昔单抗的经验，重点关注临床实践中调整方案的安全性和管理效果。 方法：本研究通过单中心真实世界数据，介绍了我们为减轻上述毒性而实施的主动管理方案（"VYLOY项目"）的经验。我们采用标准化的阶梯式输注方案及止吐预处理以降低输注相关恶心呕吐。研究纳入接受佐贝妥昔单抗联合化疗的CLDN18.2阳性晚期胃或胃食管结合部腺癌患者。 结果：共纳入24例患者。中位输注时长为215分钟，输注中断率为25.0%。在第一周期中，62.5%的患者出现输注相关不良事件，主要为1级恶心（54%）和呕吐（25%）。一线治疗患者中57%出现≥2级低白蛋白血症，可能与药物诱导的胃炎及胃肠道蛋白丢失相关。主动止吐支持与输注速率调整显著降低了后续周期的输注中断率（10.9%）。未接受胃切除术的患者恶心呕吐发生率更高，证实了胃在毒性介导中的作用。 结论：我们的结果表明，主动管理策略可提升佐贝妥昔单抗的安全性和耐受性，特别是在真实世界实践中能有效降低输注相关毒性。
Practical Management of Zolbetuximab Administration: The Project VYLOY Initiative
肿瘤(癌症)患者之家