Background
Phase III RCT, N=529, stage II or III gastric cancer (Japan), curative gastrectomy with D2 or more extensive lymph-node dissection completed within 6 weeks before enrollment. ACTS-GC (Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer) tested oral S-1 adjuvant monotherapy for 1 year vs surgery alone.
Interventions and follow up
Arm A: S-1 orally twice daily (dose by BSA: 40 mg bid for BSA <1.25 m², 50 mg bid for 1.25–1.5 m², 60 mg bid for ≥1.5 m²) days 1–28 q6wk × 8 cycles (1 year total)
Arm B: Surgery alone (observation, no adjuvant chemotherapy)
Primary endpoint: Overall survival
mFollow up: 5 yr (final analysis)
Arm B: Surgery alone (observation, no adjuvant chemotherapy)
Primary endpoint: Overall survival
mFollow up: 5 yr (final analysis)
Results
3-yr OS: 80.1% vs 70.1%, HR 0.68, 95% CI 0.52–0.87, P=.003
5-yr OS: 71.7% vs 61.1%, HR 0.67, 95% CI 0.54–0.83, P=.003
5-yr DFS: 64.2% vs 53.1%, HR 0.65, 95% CI 0.53–0.79, P<.001
5-yr OS: 71.7% vs 61.1%, HR 0.67, 95% CI 0.54–0.83, P=.003
5-yr DFS: 64.2% vs 53.1%, HR 0.65, 95% CI 0.53–0.79, P<.001
Adverse events
GI (grade ≥3): Anorexia 6.0%, nausea 3.7%, diarrhea 3.1%
Constitutional (grade ≥3): Fatigue 2.5%
Overall: Low severe toxicity; dose reductions in 38%, treatment discontinuation in 22%; no treatment-related deaths
Constitutional (grade ≥3): Fatigue 2.5%
Overall: Low severe toxicity; dose reductions in 38%, treatment discontinuation in 22%; no treatment-related deaths
Conclusions
One year of adjuvant S-1 significantly improved OS and DFS in Japanese patients with stage II/III gastric cancer after D2 gastrectomy (5-yr OS 71.7% vs 61.1%, HR 0.67), establishing S-1 as standard adjuvant therapy in Japan following curative resection.
Key Limitations
Key Limitations: Japanese patients only; S-1 tolerability is lower in Western patients (DPD polymorphism differences leading to increased toxicity). D2 dissection required — not standard in all Western centers. No comparison to CAPOX (CLASSIC) or perioperative FLOT. No biomarker selection (HER2, MSI). Surgery-alone control is now substandard in most settings. Adjuvant monotherapy may be insufficient in high-risk subgroups.
Clinical Context
S-1 adjuvant monotherapy after D2 gastrectomy is standard in Japan for stage II/III gastric cancer. In Korea and other Asian countries, CAPOX (CLASSIC trial) is also used. In Western countries, perioperative FLOT (FLOT4 trial) is preferred over adjuvant-only approaches. S-1 combined with oxaliplatin (SOX) explored in ARTIST II. Adjuvant nivolumab after pCR not achieved post-CRT is now also investigated.
References