A randomised phase II study of oxaliplatin/5-FU (mFOLFOX) versus irinotecan/5-FU (mFOLFIRI) chemotherapy in locally advanced or metastatic biliary tract cancer refractory to first-line gemcitabine/cisplatin chemotherapy

In locally advanced or metastatic biliary tract cancer (BTC), second-line chemotherapy is challenging after progression from first-line gemcitabine/cisplatin. This study evaluated whether irinotecan/5-fluorouracil (5-FU; mFOLFIRI) was superior to oxaliplatin/5-FU (mFOLFOX) as a second-line treatment in BTC.Patients diagnosed with BTC with disease progression after prior gemcitabine/cisplatin were randomised (1:1) to either mFOLFOX (control arm) or mFOLFIRI (experimental arm). Randomisation was stratified by tumour location (intrahepatic versus extrahepatic versus gallbladder versus ampulla of Vater) and ECOG performance status (0, 1 versus 2). The primary endpoint was the overall survival (OS) rate at 6 months.In total, 120 patients were enrolled and 118 patients were randomised (mFOLFOX n = 59, mFOLFIRI n = 59). The baseline characteristics were well balanced between the two arms. The tumour location was intrahepatic bile duct in 48 patients (40.7%), extrahepatic bile duct in 29 patients (24.6%), gallbladder in 35 patients (29.7%) and ampulla of Vater in 6 patients (5.1%). At a median follow-up duration of 25.8 months, the 6-month OS rate was 54.1% in mFOLFOX and 44.1% in mFOLFIRI (p = 0.677). The median OS was 6.3 months (95% CI, 4.4-8.2) in mFOLFOX and 5.7 months (95% CI, 4.7-6.7) in mFOLFIRI (p = 0.677). The median progression-free survival was 2.8 months (95% CI, 2.3-3.3) in mFOLFOX and 2.1 months (95% CI, 1.1-3.1) in mFOLFIRI (p = 0.974). Of the 101 evaluable patients, the objective response rate and disease control rate were 5.9% and 66.7% in mFOLFOX and 4.0% and 64.0% in mFOLFIRI (p = 0.663 and p = 0.778, respectively). Peripheral neuropathy (37.5% versus 5.2%) and thrombocytopenia (35.7% versus 15.5%) in mFOLFOX and vomiting (19.0% versus 1.8%) and cholangitis (10.3% versus 0.0%) in mFOLFIRI occurred more frequently. No chemotherapy-related death was reported.In the second-line treatment of BTC, mFOLFIRI was not superior to mFOLFOX. However, mFOLFIRI was tolerable and showed comparable efficacy to mFOLFOX. Adverse events were different between the two arms. CLINICALTRIALS.NCT03464968.