Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma

Author(s): Guo-Ming Shi, M.D.1,2,3; Xiao-Yong Huang, M.D.1; Fei Liang, M.D.4; Xiao Liang, M.D.5; Rui Dong, M.D.6; Qing-Hai Ye, M.D.1; Qiang Gao, M.D.1; Yuan Ji, M.D.7; Zheng-Ping Yu, M.D.8; Wen-Long Zhai, M.D.9; Jia-Cheng Lu, M.D.1; Xiao-Wu Li, M.D.10; Fu-Bao Liu, M.D.11; Kui Wang, M.D.12; Wei Yang, M.D.13; Jia-Lin Zhang, M.D.14; Zhi-Qiang Hu, M.D.1; Shuang-Jian Qiu, M.D.1; Xiao-Ying Wang, M.D.1; Xin-Rong Yang, M.D.1; Hui-Chuan Sun, M.D.1; Ying-Hong Shi, M.D.1; Zhen-Bin Ding, M.D.1; Wei-Ren Liu, M.D.1; Xiao-Wu Huang, M.D.1; Cheng Huang, M.D.1; Ying-Hao Shen, M.D.1; Jian Sun, M.D.1; Yi-Feng He, M.D.1; Yuan-Fei Peng, M.D.1; Yang Xu, M.D.1; Jian-Jun Zou, M.D.15; Jian Zhou, M.D.1,2; Jia Fan, M.D.1,2; the ZSAB Study Group*;
Source: DOI: 10.1056/NEJMoa2513918

Dr. Anjan Patel's Thoughts

This ZSAB‑neoGOLP trial is one of the first randomized neoadjuvant studies in high‑risk resectable intrahepatic cholangiocarcinoma. Neoadjuvant GOLP (gem‑ox + lenvatinib + toripalimab) nearly doubled median event‑free survival, 18.0 vs 8.7 months—and significantly reduced early recurrence, with a strong EFS P<0.001. Two‑year overall survival (OS) numerically favored the neoadjuvant arm (79% vs 61%), though it didn’t cross the stringent interim boundary. Toxicity was manageable (≈28% grade ≥3 during neoadjuvant therapy) and surgery remained feasible, making this a compelling strategy for high‑risk intrahepatic cholangiocarcinoma (ICC) pending longer follow‑up and approval.

BACKGROUND

No neoadjuvant treatment has been considered to be standard therapy for patients with resectable intrahepatic cholangiocarcinoma with high-risk factors for recurrence. The GOLP regimen (gemcitabine–oxaliplatin, lenvatinib, and an anti–programmed death 1 antibody) has shown promising efficacy with a manageable safety profile in advanced intrahepatic cholangiocarcinoma and biliary tract cancer.

METHODS

In a phase 2–3 trial, we randomly assigned, in a 1:1 ratio, patients with resectable high-risk intrahepatic cholangiocarcinoma to the neoadjuvant group (intravenous gemcitabine–oxaliplatin plus toripalimab every 3 weeks for three cycles and oral lenvatinib once daily for 9 weeks, followed by curative resection) or the control group (curative resection and no neoadjuvant treatment). All patients received adjuvant capecitabine for eight cycles after surgery. The primary end point was event-free survival. Secondary end points included overall survival and safety. Research Summary Neoadjuvant GOLP in Intrahepatic Cholangiocarcinoma

RESULTS

A total of 178 patients underwent randomization (88 patients to the neoadjuvant group and 90 to the control group). the interim analysis a median follow-up of 16.9 months, the median event-free survival was significantly longer in the neoadjuvant group (18.0 months; 95% confidence interval [CI], 13.8 to 27.6) than in the control group (8.7 months; 95% CI, 7.2 to 12.4) (P

CONCLUSIONS

Neoadjuvant GOLP led to significantly longer event-free survival than control therapy, with mainly low-grade adverse events, among patients with resectable high-risk intrahepatic cholangiocarcinoma. (Funded by the Clinical Research Plan of Shanghai Hospital Development Center and others; ZSAB-neoGOLP ClinicalTrials.gov number, NCT04669496.)

Author Affiliations

1Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai; 2Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai; 3Longevity and Aging Institute of Fudan University, Shanghai; 4Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai; 5Zhejiang Key Laboratory of Multiomics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; 6Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China; 7Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai; 8Department of Hepatobiliary Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; 9Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 10Department of Hepatobiliary Surgery, Shenzhen General Hospital of Shenzhen University, Shenzhen, China; 11Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China; 12Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai; 13Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China; 14Department of Hepatobiliary Surgery, First Affiliated Hospital of China Medical University, Shenyang, China; 15Shanghai Junshi Biosciences, Shanghai

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles