Background
Phase III RCT (CLASSIC). 1035 patients with stage II–IIIB gastric cancer after curative D2 gastrectomy at 35 centers in China, South Korea, and Taiwan. Randomized 1:1 to adjuvant CAPOX vs observation. 5-year follow-up report.
Interventions and follow up
Arm A: Adjuvant CAPOX — capecitabine 1000 mg/m² BID d1–14 + oxaliplatin 130 mg/m² d1, q3wks × 8 cycles (6 months)
Arm B: Observation
Primary endpoint: 3-year DFS
Median follow-up: 62.4 months
Arm B: Observation
Primary endpoint: 3-year DFS
Median follow-up: 62.4 months
Results
5-year DFS: 68% vs 53%, HR 0.58 (95% CI 0.47–0.72), P<.0001
5-year OS: 78% vs 69%, HR 0.66 (95% CI 0.51–0.85), P=.0015
5-year OS: 78% vs 69%, HR 0.66 (95% CI 0.51–0.85), P=.0015
Adverse events
Overall: Grade 3/4 toxicities occurred predominantly in the CAPOX arm; no additional AE data were collected beyond the primary analysis timepoint.
Most common grade 3/4 with CAPOX: Nausea, neutropenia, and peripheral neuropathy.
Most common grade 3/4 with CAPOX: Nausea, neutropenia, and peripheral neuropathy.
Conclusions
Adjuvant CAPOX significantly improved 5-year DFS (68% vs 53%) and OS (78% vs 69%) after D2 gastrectomy in stage II–IIIB gastric cancer, confirming durable benefit of postoperative chemotherapy without radiation in the setting of adequate nodal dissection.
Key Limitations
Key Limitations: Asian-only population — results may not directly apply to Western gastric cancer, which has higher rates of proximal/GEJ tumors and different biology. CAPOX completion rates after D2 surgery were not reported in detail. No comparison with perioperative FLOT or chemoradiotherapy. The observation-arm DFS of 53% at 5 years reflects outcomes after adequate D2 surgery in an Asian population, which may differ from Western surgical outcomes.
Clinical Context
CLASSIC provides the strongest evidence for postoperative CAPOX after D2 gastrectomy in Asian patients and is a standard of care in Korea, China, and Taiwan for stage II–III gastric cancer. S-1 monotherapy (ACTS-GC) is an alternative in Japan. In the West, perioperative FLOT (FLOT4) is preferred per ASCO and ESMO guidance, as it integrates chemotherapy before and after surgery and avoids post-gastrectomy compliance issues.
References