Adjuvant S-1 vs Observation for Resected Biliary Tract Cancer

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In a Japanese phase III trial (JCOG1202, ASCOT) reported in The Lancet, Nakachi et al found that adjuvant S-1 was associated with significantly improved overall survival vs observation in patients with resected biliary tract cancer.

Study Details

The multicenter, open-label trial included 440 patients with resected extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma who had undergone no local residual or microscopic residual tumor resection. They were randomly assigned between September 2013 and June 2018 to receive S-1 at 40, 50, or 60 mg (according to body surface area) twice daily for 4 weeks followed by 2 weeks off for four cycles (n = 218) or observation (n = 222). The primary endpoint was overall survival in the intent-to-treat population.

Overall Survival

At data cutoff in June 2021, median duration of follow-up was 45.4 months (interquartile range = 32.1–60.1 months). Median overall survival was not estimable (95% confidence interval [CI] = 5.2 years to not estimable) in the S-1 group vs 6.1 years (95% CI = 4.2 years to not estimable) in the observation group (hazard ratio [HR] = 0.69, 95% CI = 0.51–0.94, P = .0080). Rates at 3 years were 77.1% (95% CI = 70.9%–82.1%) vs 67.6% (95% CI = 61.0%–73.3%).


  • Adjuvant S-1 significantly improved overall survival vs observation.
  • Median overall survival was not estimable vs 6.1 years; 3-year rates were 77.1% vs 67.6%.

Median relapse-free survival was 5.3 years (95% CI = 4.1–6.1 years) in the S-1 group vs 3.5 years (95% CI = 2.0 years to not estimable) in the observation group (HR = 0.80, 95% CI = 0.61–1.04, P = .088). Rates at 3 years were 62.4% (95% CI = 55.6%–68.4%) vs 50.9% (95% CI = 44.1%–57.2%).

Among patients who had disease relapse, 83 (86%) of 96 patients in the S-1 group and 102 (89%) of 115 in the observation group received subsequent anticancer treatment, most commonly systemic chemotherapy (77% of those receiving subsequent therapy in both groups).

Adverse Events

Adverse events of any grade that occurred in ≥ 30% of patients in the S-1 group were decreased white blood cell count, decreased neutrophils, anemia, decreased platelets, hypoalbuminemia, increased alkaline phosphatase, increased aspartate aminotransferase, increased alanine aminotransferase, fatigue, anorexia, and skin hyperpigmentation. The most common grade 3 or 4 adverse events in the S-1 group were decreased neutrophils (14%), biliary tract infection (7%), and anemia (4%).

Of four grade 4 events that occurred in the S-1 group, two were considered related to treatment (myocardial infarction and Guillain-Barré syndrome).  No treatment-related deaths occurred.   

The investigators concluded, “Although long-term clinical benefit would be needed for a definitive conclusion, a significant improvement in survival suggested adjuvant S-1 could be considered a standard of care for resected biliary tract cancer in Asian patients.”

Kohei Nakachi, MD, of the Department of Medical Oncology, Tochigi Cancer Center, Utsunomiya, is the corresponding author for The Lancet article.

Disclosure: The study was funded by the National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan. For full disclosures of the study authors, visit

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