Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma

BACKGROUND: No neoadjuvant treatment has been considered to be standard therapy for patients with resectable intrahepatic cholangiocarcinoma with high-risk factors for recurrence. The GOLP regimen (gemcitabine-oxaliplatin, lenvatinib, and an anti-programmed death 1 antibody) has shown promising efficacy with a manageable safety profile in advanced intrahepatic cholangiocarcinoma and biliary tract cancer. METHODS: In a phase 2-3 trial, we randomly assigned, in a 1:1 ratio, patients with resectable high-risk intrahepatic cholangiocarcinoma to the neoadjuvant group (intravenous gemcitabine-oxaliplatin plus toripalimab every 3 weeks for three cycles and oral lenvatinib once daily for 9 weeks, followed by curative resection) or the control group (curative resection and no neoadjuvant treatment). All patients received adjuvant capecitabine for eight cycles after surgery. The primary end point was event-free survival. Secondary end points included overall survival and safety. RESULTS: A total of 178 patients underwent randomization (88 patients to the neoadjuvant group and 90 to the control group). At the interim analysis at a median follow-up of 16.9 months, the median event-free survival was significantly longer in the neoadjuvant group (18.0 months; 95% confidence interval [CI], 13.8 to 27.6) than in the control group (8.7 months; 95% CI, 7.2 to 12.4) (P