Background
Phase III open-label RCT (JCOG1202/ASCOT), N=440 patients with biliary tract cancer (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer) following curative-intent R0 resection. Stratified by tumor site and institution. Conducted across Japan. Enrolled 2012–2018.
Interventions and follow up
Arm A: S-1 (tegafur/gimeracil/oteracil) 80–120 mg/day based on BSA, days 1–28 of a 42-day cycle × 4 cycles (6 months)
Arm B: Surgery alone (observation)
Primary endpoint: Overall survival (OS)
Median follow-up: 36 months
Arm B: Surgery alone (observation)
Primary endpoint: Overall survival (OS)
Median follow-up: 36 months
Results
OS: 3-year OS 77.1% vs 67.6%, HR 0.69 (95% CI 0.51–0.95), P=.008
RFS: HR 0.79 (95% CI 0.61–1.02), P=.069 — not significant
RFS: HR 0.79 (95% CI 0.61–1.02), P=.069 — not significant
Adverse events
Gastrointestinal: Grade ≥3 nausea/vomiting 5%, diarrhea 4%, anorexia 3%.
Hematologic: Grade ≥3 neutropenia 3%.
Overall: Grade ≥3 AEs in 33% of Arm A; S-1 generally well tolerated, completion rate ~80% of planned cycles.
Hematologic: Grade ≥3 neutropenia 3%.
Overall: Grade ≥3 AEs in 33% of Arm A; S-1 generally well tolerated, completion rate ~80% of planned cycles.
Conclusions
Adjuvant S-1 significantly improved OS compared to observation in R0-resected biliary tract cancer, with a 10-percentage-point improvement in 3-year OS (77.1% vs 67.6%; HR 0.69, P=.008). This is one of the first phase III trials to demonstrate a statistically significant OS benefit from adjuvant chemotherapy in resected BTC.
Key Limitations
Trial conducted entirely in Japan — S-1 is primarily used in Asia (not standard in Western practice), limiting direct generalizability to Western populations. RFS benefit did not reach statistical significance (HR 0.79, P=.069), though OS did — this paradox may reflect lead-time bias or non-cancer mortality differences. Restricted to R0 resections only; the BILCAP trial included both R0 and R1 resections. Biological heterogeneity across BTC subsites may obscure subsite-specific benefits. Cross-trial comparison with BILCAP (capecitabine, Western population) is limited by different drugs, populations, and resection criteria.
Clinical Context
ASCOT/JCOG1202 is the second adjuvant trial to demonstrate OS benefit in resected BTC (after BILCAP), solidifying adjuvant chemotherapy as standard of care. In Japan and parts of Asia, S-1 has become a standard adjuvant option. In the West, capecitabine (based on BILCAP per-protocol analysis) remains the dominant choice. ESMO guidelines list both capecitabine and S-1 as acceptable adjuvant options for resected BTC. Neither agent is FDA-approved specifically for this indication. Emerging data from the ACTICCA-1 trial (gemcitabine+cisplatin adjuvant) are awaited as a potential future standard.
References