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/m2 of gemcitabine on day 1 and 80?mg/m2/day of S-1 (80/100/120?mg for patients with body surface '1.25/ ?1.25 and '1.5/ ?1.5?m2 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. ? 2020 The Authors. Liver International published by John Wiley & Sons Ltd