Pathological Complete Response Following mFOLFOX6 Plus Zolbetuximab and Conversion Surgery in Initially Unresectable...

Zolbetuximab plus platinum-fluoropyrimidine chemotherapy has emerged as an important first-line treatment option for patients with claudin 18.2 (CLDN18.2)-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma. However, pathological complete response after zolbetuximab-based induction therapy followed by conversion surgery has rarely been documented, particularly in patients with peritoneal dissemination and malignant ascites. A man in his early 50s with Eastern Cooperative Oncology Group performance status 0 was referred to our hospital with scirrhous-type gastric cancer. Initial evaluation revealed initially unresectable advanced gastric cancer with peritoneal dissemination and cytologically confirmed malignant ascites. Gastric biopsy showed poorly differentiated adenocarcinoma with signet-ring cell features. The tumor was HER2 IHC 1+, strongly CLDN18.2-positive by the VENTANA CLDN18 (43-14 A) RxDx Assay, with 90% of viable tumor cells showing 2+/3 + membranous staining, proficient mismatch repair, and PD-L1 CPS ≥ 10. First-line mFOLFOX6 plus zolbetuximab was administered every 2 weeks without dose reduction or treatment delay. After six cycles, computed tomography and esophagogastroduodenoscopy showed marked improvement. After nine cycles, conversion surgery with total gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction was performed. Intraoperative lavage cytology was negative. Final pathology showed ypT0N0, 0/20 lymph nodes, and TRG 1a/Grade 3, consistent with pathological complete response. This case suggests that mFOLFOX6 plus zolbetuximab may induce deep radiological, endoscopic, cytological, and pathological responses and may enable R0 conversion surgery in carefully selected patients with CLDN18.2-positive initially unresectable advanced gastric cancer.