Two cases of protein-losing enteropathy induced by zolbetuximab in patients with unresectable advanced gastric cancer

Abstract The GLOW and SPOTLIGHT trials have demonstrated the efficacy of chemotherapy plus zolbetuximab for HER2-negative, claudin-18 isoform 2 (CLDN18.2)–positive unresectable advanced or recurrent gastric cancer (AGC)/gastroesophageal junction cancer. However, data on adverse events in real-world clinical practice are still insufficient. Specifically, gastritis and protein-losing enteropathy (PLE), which were not evident in either trials, are not generally recognized. This paper reports on the notable clinical course and examination findings of two cases of PLE observed in patients with unresectable AGC who were administered zolbetuximab. Case 1 involved a 66-year-old woman with HER2-negative, CLDN18.2-positive unresectable advanced gastric cancer (cT4aN1M1) with peritoneal dissemination. As a fifth-line treatment, she underwent combination therapy with capecitabine, oxaliplatin, and zolbetuximab (CAPEOX + Zolbe). Case 2 involved a 58-year-old woman with HER2-negative, CLDN18-positive gastric cancer (pT1aN3bM1) with extra-regional lymph node metastasis. After undergoing robot-assisted distal gastrectomy, she commenced CAPEOX + Zolbe therapy. In both cases, following the initiation of CAPEOX + Zolbe therapy, serum albumin levels decreased from 3.5 g/dL pre-treatment to 2.2 g/dL. Upper gastrointestinal endoscopy revealed diffuse redness and edema of the gastric mucosa. Pathological histological examination of the gastric mucosal biopsy also revealed findings consistent with PLE. A technetium-99m–labeled human serum albumin scintigraphy demonstrated leakage of Tc-99m albumin into the gastrointestinal tract, leading to a diagnosis of PLE. In the two cases we experienced, we observed gastritis and PLE caused by zolbetuximab. These adverse events are not widely recognized among clinicians. However, when hypoalbuminemia occurs during zolbetuximab administration, this diagnosis should be considered.