Neoadjuvant GOLP Demonstrates Efficacy, Safety in High-Risk Intrahepatic Cholangiocarcinoma

Key Clinical Summary: 

• Design/Population: In this phase 2/3 randomized trial, 178 patients with high-risk intrahepatic cholangiocarcinoma received either neoadjuvant GOLP or upfront surgery. All patients received adjuvant capecitabine following surgery.
• Key Outcomes: Neoadjuvant GOLP significantly improved event-free survival. Overall survival numerically favored the neoadjuvant group, although the prespecified statistical threshold was not met.
• Clinical Relevance: These findings support the potential role of neoadjuvant chemoimmunotherapy in high-risk intrahepatic cholangiocarcinoma. GOLP may represent a new strategy to improve outcomes in this population pending further validation.

Results from a phase 2/3 trial demonstrate that neoadjuvant gemcitabine, oxaliplatin, lenvatinib, and toripalimab (GOLP) significantly improves survival compared with surgery alone among patients with high-risk resectable intrahepatic cholangiocarcinoma.

“No neoadjuvant treatment has been considered to be standard therapy for patients with resectable intrahepatic cholangiocarcinoma with high-risk factors for recurrence,” stated Guo-Ming Shi, MD, Fudan University, Shanghai, China, and coauthors. “The GOLP regimen has shown promising efficacy with a manageable safety profile in advanced intrahepatic cholangiocarcinoma and biliary tract cancer.”

In this study, 178 patients were randomized 1:1 to receive neoadjuvant GOLP every 3 weeks for 3 cycles plus lenvatinib for 9 weeks followed by surgical resection (n = 88) or upfront surgery (n = 90). All patients received adjuvant capecitabine after surgery. The primary end point was event-free survival (EFS). Secondary end points included overall survival (OS) and safety.

At a median follow-up of 16.9 months, median EFS was 18 months in the neoadjuvant arm and 8.7 months in the control arm (P < .001). At 24 months, OS rate was 79% in the neoadjuvant arm and 61% in the control arm (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.23 to 0.79; P = .005), although the prespecified threshold for statistical significance was not met.

Any-grade adverse events were reported in 97% of patients in the neoadjuvant arm and 70% in the control arm. During the neoadjuvant phase, grade ≥ 3 adverse events were reported in 28% of patients with grade ≥ 3 treatment-related adverse events reported in 26% of patients. No treatment-related deaths were reported. 

As Dr Shi et al. concluded, “neoadjuvant GOLP led to significantly longer [EFS] than control therapy, with mainly low-grade adverse events, among patients with resectable high-risk intrahepatic cholangiocarcinoma.” 

Source: 

Shi GM, Huang XY, Liang F, et al. Neoadjuvant GOLP in resectable high-risk intrahepatic cholangiocarcinoma. N Engl J Med. Published online: March 4, 2026. doi:10.1056/NEJMoa2513918