Neoadjuvant GOLP Boosts Event-Free Survival in High-Risk Intrahepatic Cholangiocarcinoma: NEJM Study
China: A neoadjuvant combination regimen comprising chemotherapy, targeted therapy, and immunotherapy has demonstrated significant clinical benefit in patients with resectable high-risk intrahepatic cholangiocarcinoma (ICC), a study published in the New England Journal of Medicine has revealed.
The study was conducted by Guo-Ming Shi from the Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai, and colleagues.
Intrahepatic cholangiocarcinoma is an aggressive primary liver malignancy with high rates of postoperative recurrence, particularly among patients with adverse prognostic features. Despite curative-intent surgery being the standard of care for resectable disease, no preoperative (neoadjuvant) therapy has been widely accepted as standard treatment for patients at high risk of relapse.
The investigators evaluated the GOLP regimen — a combination of gemcitabine and oxaliplatin chemotherapy with lenvatinib and the anti–programmed death 1 (PD-1) antibody toripalimab — in a phase 2–3 randomized trial. Previous studies had suggested encouraging activity and manageable toxicity of this combination in advanced biliary tract cancers.
In the trial, 178 patients with resectable high-risk ICC were randomly assigned in a 1:1 ratio to receive either neoadjuvant GOLP followed by surgery or immediate surgery alone. The neoadjuvant protocol included three cycles of intravenous gemcitabine–oxaliplatin plus toripalimab every 3 weeks, followed by 9 weeks of daily oral lenvatinib, after which patients underwent curative resection. Patients in the control arm proceeded directly to surgery without preoperative therapy. Following surgery, all participants received eight cycles of adjuvant capecitabine.
The primary endpoint was event-free survival, while secondary endpoints included overall survival and safety outcomes.
The key findings were as follows:
- At a median follow-up of 16.9 months, interim analysis demonstrated a significant improvement in event-free survival with neoadjuvant GOLP compared to surgery alone.
- Median event-free survival was 18.0 months in the neoadjuvant group versus 8.7 months in the control group.
- Overall survival at 24 months was 79% in the neoadjuvant arm compared with 61% in the surgery-alone group.
- The hazard ratio for death was 0.43, suggesting a notable reduction in mortality risk; however, this did not meet the prespecified threshold for statistical significance at the interim analysis.
- Adverse events were reported in 97% of patients receiving neoadjuvant therapy and in 70% of those undergoing surgery alone.
- During the neoadjuvant phase, grade 3 or higher adverse events occurred in 28% of patients, while treatment-related grade 3 or higher events were observed in 26%.
- No treatment-related deaths were recorded, and the majority of adverse events were low grade.
The authors concluded that neoadjuvant GOLP significantly prolonged event-free survival in patients with resectable high-risk ICC, with an acceptable safety profile. These findings suggest that a multimodal preoperative approach may represent a promising new strategy to reduce recurrence and improve outcomes in this high-risk population.
Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2513918
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