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ZSAB-neoGOLP

Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma (ZSAB-neoGOLP)

Phase 2/3N = 178NCT04669496

Population
Patients with resectable intrahepatic cholangiocarcinoma and high-risk recurrence factors (definition not given in the abstract); 178 randomised.
Design
Randomised phase 2-3 trial (registry: seamless phase II-III, no masking). Patients with resectable high-risk intrahepatic cholangiocarcinoma were randomly assigned 1:1 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 to the control group (curative resection and no neoadjuvant treatment). All patients received adjuvant capecitabine for eight cycles after surgery. Primary end point event-free survival; secondary end points included overall survival and safety. 178 patients were randomised (88 and 90). Interim analysis at a median follow-up of 16.9 months. ClinicalTrials.gov NCT04669496: enrolment 178 (actual), status active not recruiting, no results posted, one listed site (Zhongshan Hospital, China).
Primary endpoint
EFS
Arms
  • Curative resection, no neoadjuvant treatment (control, n = 90): Curative resection and no neoadjuvant treatment, then adjuvant capecitabine for eight cycles
  • Neoadjuvant GOLP then resection (experimental, n = 88): Gemcitabine-oxaliplatin plus toripalimab every 3 weeks for three cycles and oral lenvatinib once daily for 9 weeks, then curative resection and adjuvant capecitabine for eight cycles
People
Shi GM, ZSAB Study Group
Δ median EFS+9.3 monthsOSHR 0.43 (95% CI 0.23–0.79)Δ 24-month OS+18 points
Show the numbers
Results reported for ZSAB-neoGOLP
EndpointAnalysisNeoadjuvant GOLP then resectionCurative resection, no neoadjuvant treatmentEffect
EFSRandomised patients (analysis population not stated in the abstract)As described in the registry record: from randomisation to disease progression that prevents radical surgery, local or distant recurrence, a second primary tumour, or death (the registry wording is 'death due to various causes').interimmedian follow-up 16.9 monthsShi 2026median 18 months (13.8–27.6)median 8.7 months (7.2–12.4)P<0.001Primary endpoint at the interim analysis; no hazard ratio for event-free survival is given in the abstract. Adverse events occurred across all treatment phases in 97% of the neoadjuvant group and 70% of the control group. During the neoadjuvant phase, adverse events of grade 3 or higher occurred in 28% of patients and treatment-related adverse events of grade 3 or higher in 26%; no treatment-related adverse event led to death.
OSRandomised patients (analysis population not stated in the abstract)interimmedian follow-up 16.9 monthsShi 202679% at 2 y (70–90%)61% at 2 y (50–75%)HR 0.43 (95% CI 0.23–0.79)P=0.005Overall survival was a secondary endpoint. The abstract states the p-value did not meet the significance criterion (two-sided alpha 0.0019). The hazard ratio is for death.
Results reported for ZSAB-neoGOLP
EndpointAnalysisNeoadjuvant GOLP then resectionCurative resection, no neoadjuvant treatmentEffect
EFSRandomised patients (analysis population not stated in the abstract)As described in the registry record: from randomisation to disease progression that prevents radical surgery, local or distant recurrence, a second primary tumour, or death (the registry wording is 'death due to various causes').interimmedian follow-up 16.9 monthsShi 2026median 18 months (13.8–27.6)median 8.7 months (7.2–12.4)P<0.001Primary endpoint at the interim analysis; no hazard ratio for event-free survival is given in the abstract. Adverse events occurred across all treatment phases in 97% of the neoadjuvant group and 70% of the control group. During the neoadjuvant phase, adverse events of grade 3 or higher occurred in 28% of patients and treatment-related adverse events of grade 3 or higher in 26%; no treatment-related adverse event led to death.
OSRandomised patients (analysis population not stated in the abstract)interimmedian follow-up 16.9 monthsShi 202679% at 2 y (70–90%)61% at 2 y (50–75%)HR 0.43 (95% CI 0.23–0.79)P=0.005Overall survival was a secondary endpoint. The abstract states the p-value did not meet the significance criterion (two-sided alpha 0.0019). The hazard ratio is for death.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.430.23–0.79
Illustrative — modelled from reported values, not trial data. EFS, interim.
0%25%50%75%100%010203040Months (modelled)
  • Neoadjuvant GOLP then resection (experimental)
  • Curative resection, no neoadjuvant treatment (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsNeoadjuvant GOLP then resectionCurative resection, no neoadjuvant treatment
0100.0%100.0%
1165.5%41.6%
2341.2%16.0%
3427.0%6.7%
4517.7%2.8%
Primary publication: Shi GM, Huang XY, Liang F, Liang X, Dong R, Ye QH, et al. Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma. N Engl J Med. 2026;394(10):983-995. PubMedDOI

Appears in

Sources

  1. Shi GM, Huang XY, Liang F, Liang X, Dong R, Ye QH, et al. Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma. N Engl J Med. 2026;394(10):983-995.

    PubMedDOI