Background
Phase II-III, N=178 (88 neoadjuvant, 90 control). Resectable high-risk intrahepatic cholangiocarcinoma (CNLC stage Ib-IIIa) at intermediate-to-high recurrence risk. Tested perioperative GOLP (gemcitabine-oxaliplatin + lenvatinib + toripalimab) added to surgery to address high post-resection recurrence.
Interventions and follow up
Arm A: Neoadjuvant gemcitabine-oxaliplatin (Q3W x 3 cycles) + toripalimab + lenvatinib (9 weeks), then surgery, then adjuvant capecitabine x 8 cycles
Arm B: Surgery alone, then adjuvant capecitabine x 8 cycles
Primary endpoint: Event-free survival (EFS)
Median follow up: 16.9 months at interim analysis
Arm B: Surgery alone, then adjuvant capecitabine x 8 cycles
Primary endpoint: Event-free survival (EFS)
Median follow up: 16.9 months at interim analysis
Results
Event-free survival: Median 18.0 vs 8.7 months, P<.001
Overall survival at 24 months: 79% vs 61%, HR 0.43, 95% CI 0.23-0.79, P=.005
Overall survival at 24 months: 79% vs 61%, HR 0.43, 95% CI 0.23-0.79, P=.005
Adverse events
Overall: Grade ≥3 AE 28% during neoadjuvant phase; grade ≥3 treatment-related AE 26%; most AEs low-grade
Serious/fatal: 2 treatment-related deaths (hepatic failure; combined hepatic/renal failure)
Serious/fatal: 2 treatment-related deaths (hepatic failure; combined hepatic/renal failure)
Conclusions
Neoadjuvant GOLP followed by surgery significantly prolonged EFS and improved OS versus surgery alone in high-risk resectable intrahepatic cholangiocarcinoma, addressing the high recurrence risk in this population.
Key Limitations
Interim analysis with immature final OS; limited to intrahepatic cholangiocarcinoma (may not apply to extrahepatic or gallbladder cancers); 2 treatment-related deaths warrant careful patient selection; predominantly single-region enrollment.
Clinical Context
GOLP is among the first neoadjuvant regimens to show EFS/OS benefit in resectable high-risk biliary tract cancer. The chemotherapy + tyrosine kinase inhibitor + immunotherapy combination may reshape perioperative treatment paradigms; not yet reflected in current ESMO guidance pending mature data and regulatory review.