Multicenter phase 2-3 trial of neoadjuvant GOLP for resectable high-risk intrahepatic cholangiocarcinoma

There is no standard therapy for patients with resectable intrahepatic cholangiocarcinoma (iCCA) with high risk of recurrence. The multicenter phase 2-3 ZSAB study in China evaluated neoadjuvant GOLP (gemcitabine-oxaliplatin, lenvatinib, and an anti-PD-1 antibody) for these patients. Patients were randomized 1:1 to neoadjuvant GOLP (intravenous gemcitabine-oxaliplatin plus toripalimab every 3 weeks for three cycles and oral lenvatinib once daily for 9 weeks, followed by curative resection; n=88) or control (curative resection only; n=90). All patients received adjuvant capecitabine for eight cycles after surgery. The primary endpoint was event-free survival (EFS). At the interim analysis at a median follow-up of 16.9 months, the median EFS was significantly longer in the neoadjuvant group than in the control group (18.0 months versus 8.7 months; p<0.001); whereas the overall survival rate at 24 months was 79% versus 61% (p=0.005) which did no meet the significance criterion (two-sided alpha, 0.0019). Across all treatment phases, adverse events occurred in 97% of the patients in the neoadjuvant group and 70% of those in the control group. During the neoadjuvant phase, adverse events of grade 3 or higher occurred in 28% of the patients; no treatment-related adverse event led to death. The authors conclude that neoadjuvant GOLP led to significantly longer EFS than control therapy, with mainly low-grade adverse events, among patients with resectable high-risk iCCA (quick take video summary).