Neoadjuvant immuno-chemotherapy combined with antiangiogenic therapy for patients with resectable high-risk intrahepatic cholangiocarcinoma and excellent performance status: interim efficacy results from the ZSAB-neoGOLP trial

The ZSAB-neoGOLP trial by Shi et al. is the first completed and reported phase II-III randomized controlled trial of neoadjuvant therapy for patients with biliary tract cancer (BTC).Importantly, it is disease-specific for intrahepatic cholangiocarcinoma (iCCA), randomizing 178 patients with this relatively rare cancer type (1).This is an impressive and clinically important achievement in light of previous trials that have included patients with BTCs arising in the gallbladder, intra-/extrahepatic bile ducts, and ampulla of Vater (2,3), despite significant biological differences between these diseases (4).The study thus represents an important milestone toward advancing care for patients with iCCA specifically.Currently, most patients undergoing surgery for iCCA experience recurrence, and median overall survival after surgery is limited to less than 5 years (4), indicating a strong rationale to develop novel strategies, including neoadjuvant treatment.The primary endpoint of the neoGOLP trial was event-free survival, defined as a composite of progression to unresectability, recurrence, development of another malignancy, or death.This choice of outcome, together with a trial population consisting of patients with iCCA and oncological high-risk criteria (clinical staging with tumor size >5 cm, multiple lesions, vascular invasion, or lymph node metastases), were likely key factors in the successful accrual and completion of the trial, as the current literature justifies a high expected event rate, with a median-event free survival time well below 1 year for the trial control arm.The NEO-GAP phase II trial employed similar high-risk criteria