Single-center retrospective cohort study of durable complete response and potential cure with systemic chemotherapy in metastatic gastric cancer

Cure of metastatic gastric or gastroesophageal junction cancer (mGC/GJEC) with systemic chemotherapy alone is rare. Although long-term follow-up of previous phase 3 trial suggests 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. A retrospective study at the National Cancer Center Hospital East (Kashiwa, Japan) investigated these characteristics. 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 treatment initiation, and remained free from disease progression for at least 1 year after treatment discontinuation. Among 1710 patients treated between April 2013 and March 2022, 51 (3%) met the criteria for potential cure. The median age was 67 years, and 72.5% were male and had single-organ metastasis. Among patients with assessable biomarker status, the proportions of positive cases were 23.5% for HER2. 23.3% for dMMR, 16.0% for CLDN18.2, and 30.0% for PD-L1 combined positive score ≥ 10. 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 authors conclude that the introduction of molecularly targeted agents and immunotherapy has expanded the chance of potential cure. The enrichment of dMMR, HER2-positive, and PD-L1 CPS-high tumors among potentially cured cases highlights the need to develop effective therapies for those lacking actionable biomarkers.