GOLP in High-Risk Resectable Intrahepatic Cholangiocarcinoma NEJM, March 2026

Introduction

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and carries a poor prognosis even after curative surgery. Recurrence rates exceed 50%, particularly in patients with high-risk features such as large tumours (>5 cm), vascular invasion, multifocal disease, lymph-node involvement, or elevated CA19-9. Until now, no neoadjuvant therapy has been established as standard treatment for resectable high-risk iCCA.

The GOLP regimen—a combination of gemcitabine–oxaliplatin chemotherapy, lenvatinib (an anti-angiogenic agent), and the PD-1 inhibitor toripalimab—has shown encouraging activity in advanced biliary tract cancers. This phase 2–3 randomised trial evaluated whether neoadjuvant GOLP before surgery could improve outcomes in patients with resectable high-risk iCCA.

Summary

In this multicenter randomised trial, 178 patients with resectable high-risk intrahepatic cholangiocarcinoma were assigned to either:

Neoadjuvant GOLP therapy followed by surgery and adjuvant capecitabine

Upfront surgery followed by adjuvant capecitabine (control group)

At a median follow-up of 16.9 months, the median event-free survival was significantly longer with neoadjuvant therapy (18.0 months) compared with the control group (8.7 months, P<0.001).

Two-year overall survival was 79% in the neoadjuvant group versus 61% in the control group, suggesting a survival advantage, although the predefined statistical threshold was not met.

The objective response rate to neoadjuvant therapy was approximately 55%, with major pathological response in 19% and pathological complete response in 5% of patients.

Adverse events occurred in 97% of patients receiving GOLP, with grade ≥3 toxicity in 28%, mainly hematologic, but no treatment-related deaths were reported.

Key Message

Neoadjuvant GOLP therapy significantly improves event-free survival in patients with resectable high-risk intrahepatic cholangiocarcinoma, suggesting a promising strategy to reduce early recurrence and potentially improve long-term outcomes.