A Phase Ii Trial Of Modified Gemcitabine Plus S-1 Combination As The First-Line Treatment In Patients With Advanced Biliary Tract Cancer.

417 Background: Gemcitabine plus platinum, notably cisplatin, is conceived as the standard regimen for advanced biliary tract cancer (ABTC) nowadays. Recent randomized phase II study (JCOG0805) showed that gemcitabine plus S-1 was more promising than S-1 alone in ABTC, and a randomized phase III, UMIN 000001685, is currently ongoing to compare the efficacy of gemcitabine plus either S-1 (GS) or cisplatin (GC) in ABTC. Herein, we report the results of a single arm phase II of modified GS in Taiwanese ABTC patients, NCT02425137. Methods: Patients with chemonaïve ABTC were eligible to receive 800mg/m 2 gemcitabine with 10 mg/m 2 /min infusion, on day 1 plus daily 80/100/120 mg of S-1 (based on BSA) days 1-10, in a 2-week cycle. With Optimal Simon’s two-stage design and (p 0 = 0.4, p 1 = 0.6) for 12-week disease control rate (proportion of patients with complete or partial response [CR/PR] or stable disease ≥ 12 weeks [SD ≥ 12weeks ]) and given error probabilities (alpha = 0.05, beta = 0.2), the null hypothesis (p 0 ) would be rejected if 24 or more patients with CR/PR/SD ≥ 12weeks were observed among 46 accruals. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. Results: Between May 2015 and April 2016, totally 46 evaluable patients were enrolled to receive a median of 9.5 cycles (range: 3-31) of modified GS. After a median of 8.7 months (95% CI, 6.7-9.1) follow-up, 10 (21.7%) patients achieved PR and additional 23 (50%) had SD > 12weeks . The median progression-free survival and overall survival was 5.6 (95% CI, 4.4-7.2) and 10.8 (95% CI, 7.6-not reached) months, respectively. All grade 3 treatment-related AEs were < 5%. The dose intensity of S-1 and gemcitabine were both more than 95%. Conclusions: By the observation of 33 patients with PR/SD ≥ 12weeks , the null hypothesis was rejected. Modified GS is an active regimen with excellent safety profiles and deserves further investigation for the management of Asian ABTC patients. Clinical trial information: NCT 02425137.