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

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.

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.

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.

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.