Durable Complete Response and Potential Cure With Systemic Chemotherapy in Metastatic Gastric Cancer: A Case Series of Patients

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PURPOSE: Cure of metastatic gastric or gastroesophageal junction cancer (mGC/GEJC) with systemic chemotherapy alone is extremely rare. Although long-term follow-up from previous phase III studies suggest that durable complete response (CR) may occur in a limited number of patients with first-line treatment, clinical characteristics of such cases remain poorly characterized. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with mGC/GEJC who received systemic chemotherapy at our institute between April 2013 and March 2022. Patients were defined as having a potential cure if they demonstrated a clinical or pathologic CR, maintained progression-free survival for more than 3 years from the treatment initiation, and remained free from disease progression for at least 1 year after treatment discontinuation. Clinicopathologic features, treatment regimens, and biomarker profiles, including human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR), programmed death ligand-1 (PD-L1), and claudin 18.2 (CLDN18.2), were analyzed. RESULTS: Fifty-one patients met the criteria for potential cure. The median age was 67 years and 72.5% of the patients were male and had single-organ metastasis. Among patients with assessable biomarker status, the proportions of positive cases were 23.5% for HER2 (n = 51), 23.3% for deficient MMR (dMMR; n = 43), 16.0% for CLDN18.2 (n = 25), and 30.0% for PD-L1 Combined Positive Score (CPS) ≥10 (n = 30). First-line therapy led to potential cure in 52.9% of patients. Ten patients were potentially cured with cytotoxic chemotherapy alone, while 23 and 26 patients received molecular targeted agents or immunotherapy, respectively. CONCLUSION: The introduction of molecular targeted agents and immunotherapy has expanded the chance of potential cure. The enrichment of dMMR, HER2-positive, and CPS-high tumors among potentially cured cases highlights the urgent need to develop effective therapies for those lacking actionable biomarkers.

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