Multicentre, phase II study of gemcitabine and S‐1 in patients with advanced biliary tract cancer: TG1308 study

BACKGROUND & AIMS: Gemcitabine plus cisplatin (GC) remains the standard, frontline therapy for advanced biliary tract cancer (ABTC). The JCOG1113 study suggested that gemcitabine plus S‐1 (GS) had noninferior median overall survival and comparable incidence of significant neutropenia as compared to GC treatments. This study evaluates the efficacy and safety of a modified GS regimen. METHODS: The eligible patients with chemonaive, measurable ABTC received 800 mg/m(2) of gemcitabine on day 1 and 80 mg/m(2)/day of S‐1 (80/100/120 mg for patients with body surface <1.25/ ≥1.25 and <1.5/ ≥1.5 m(2) respectively). The primary endpoint was the 12‐week disease control rate (12‐week DCR: objective response and stable disease ≥ 12 weeks). Per the p0 = 40% and p1 = 60% (α/β = 0.05/0.2) assumption, Simon's optimal two‐stage design indicated 12‐week DCR in ≥ 24 of 46 evaluable patients for significant activity. Tumour responses were assessed every 6 weeks. RESULTS: Fifty‐one patients were enrolled and most of them had intrahepatic cholangiocarcinoma (64.7%), metastatic disease (84.3%) and disease‐related symptoms (82.4%). On intention‐to‐treat analysis, 11 (21.6%) patients showed partial response, whereas 21 (41.2%) showed stable disease ≥ 12 weeks. The progression‐free and overall survival were 5.4 months (95% confidence interval [CI]: 3.5‐7.0), and 12.7 months (95% CI: 6.1‐15.6) respectively. The study met its primary endpoint with a 12‐week DCR of 69.6% in 46 evaluable patients. Grade 3/4 treatment‐related adverse eventsoccurred in < 6% of patients of all individual items. The mean dose intensities of S‐1 and gemcitabine were 87.1% and 92.5% respectively. CONCLUSIONS: Modified GS showed moderate efficacy with a favourable safety profile in ABTC patients, thus mandating further assessment. ClinicalTrials.gov number: NCT02425137.