← Return to [[Biliary Tract Cancer Clinical Trials]] ---- Phase II/III | Multicenter randomized trial (ZSAB Study Group) | n=178 | High-risk resectable ICC | NEJM 2026 **Shi et al.** Published in New England Journal of Medicine, 2026 [PubMed Link](https://pubmed.ncbi.nlm.nih.gov/41780001/) --- ### Essential Takeaway neoGOLP was the first randomized trial to demonstrate benefit from neoadjuvant therapy in resectable high-risk intrahepatic cholangiocarcinoma. Neoadjuvant GemOx, lenvatinib, and toripalimab significantly improved event-free survival compared with upfront surgery followed by adjuvant capecitabine. --- ### Clinical Question Does neoadjuvant GOLP improve outcomes compared with upfront surgery in patients with resectable high-risk ICC? --- ### Population Resectable ICC with at least one high-risk feature: - Tumor >5 cm - Multifocal disease - Vascular invasion - Portal lymph node metastasis - Elevated CA 19-9 --- ### Study Design Randomized 1:1 multicenter trial. #### Arm 1 — neoGOLP - Gemcitabine/oxaliplatin - Lenvatinib - Toripalimab Followed by: - Curative-intent resection - Adjuvant capecitabine #### Arm 2 — Surgery First - Immediate resection - Adjuvant capecitabine --- ### Endpoints #### Primary Endpoint - Event-free survival #### Secondary Endpoints - Overall survival - Objective response - R0 resection - Major pathologic response - Recurrence-free survival - Safety --- ### Key Results #### Event-Free Survival - 18.0 vs 8.7 months - p < 0.001 #### Overall Survival 24-month OS: - 79% vs 61% Strongly favored neoGOLP but did not meet the prespecified interim significance boundary. #### Objective Response - 55% #### Pathologic Response - Major pathologic response: 19% - Pathologic complete response: 5% #### Surgical Outcomes - Surgery performed: 97% vs 99% - R0 resection: 95% vs 93% #### Toxicity During neoadjuvant therapy: - Grade ≥3 adverse events: 28% - Grade ≥3 treatment-related adverse events: 26% - No treatment-related deaths --- ### Interpretation neoGOLP represents the strongest prospective evidence to date supporting neoadjuvant therapy for high-risk resectable ICC. Unlike NEO-GAP, which established feasibility, neoGOLP demonstrated improved event-free survival in a randomized trial. The study supports biologic selection and early systemic therapy before major hepatectomy in patients at high risk for recurrence. --- ### Important Limitations - Interim analysis - Overall survival immature - Conducted exclusively in China - Regimen may not be globally generalizable - Very high R0 rates in both arms --- ### Relationship to Other ICC Trials #### BILCAP Established adjuvant capecitabine after BTC resection. #### NEO-GAP Established feasibility of neoadjuvant chemotherapy in high-risk resectable ICC. #### neoGOLP First randomized trial demonstrating improved event-free survival with neoadjuvant therapy in high-risk resectable ICC. --- ### Practice Impact neoGOLP may shift high-risk resectable ICC toward a neoadjuvant-first paradigm, though longer follow-up and broader external validation are needed.