← Return to [[Biliary Tract Cancer Clinical Trials]] ---- Phase II | Multi-institutional single-arm feasibility trial | n=30 | Resectable high-risk ICC | Ann Surg Oncol 2023 **Maithel et al.** Published in Annals of Surgical Oncology, 2023 Enrollment: 2018–2021 [PubMed Link](https://pubmed.ncbi.nlm.nih.gov/37368098/) --- ### Essential Takeaway NEO-GAP demonstrated that neoadjuvant **gemcitabine/cisplatin/nab-paclitaxel (GAP)** is feasible and safe before resection of **high-risk intrahepatic cholangiocarcinoma**. It was not designed to prove survival benefit, but it established an important prospective foundation for neoadjuvant-first strategies in resectable high-risk ICC. --- ### Clinical Question Can neoadjuvant GAP be safely delivered before curative-intent resection in high-risk, technically resectable ICC? --- ### Population High-risk resectable ICC defined by: - Tumor >5 cm - Multifocal disease - Major vascular invasion - Regional lymph node involvement Patients had no distant metastatic disease. --- ### Study Design Single-arm phase II feasibility trial. #### Treatment 4 cycles neoadjuvant GAP: - Gemcitabine - Cisplatin - Nab-paclitaxel Followed by: - Restaging - Curative-intent resection --- ### Endpoints #### Primary Endpoint Completion of both: - neoadjuvant chemotherapy - surgical resection #### Secondary Endpoints - Toxicity - Radiographic response - R0 resection - Recurrence-free survival - Overall survival --- ### Key Results #### Feasibility - 100% completed planned chemotherapy - 73% completed chemotherapy and surgery - Primary endpoint met #### Radiographic Response - Partial response: 23% - Stable disease: 67% - Progressive disease: 10% Disease control rate: - 90% #### Surgical Outcomes Among resected patients: - R0 resection: 73% - Major postoperative complications: 0% - Median length of stay: 4 days #### Survival - Median OS, entire cohort: 24 months - Median OS, resected patients: not reached - Median RFS: 7.1 months #### Toxicity - Grade ≥3 adverse events: 33% - Most common: neutropenia - Treatment-related mortality: 0% - 50% required at least one dose reduction --- ### Interpretation NEO-GAP was a feasibility study, not a definitive efficacy trial. Its main contribution was showing that systemic therapy can be delivered upfront in high-risk ICC without compromising surgery. This supports the broader concept of biologic selection before major hepatectomy in patients at high risk for early recurrence. --- ### Important Limitations - Single-arm design - Small sample size - No surgery-first control group - Not powered for survival - Adjuvant therapy was not standardized --- ### Current Practice Relevance NEO-GAP supports consideration of neoadjuvant therapy for high-risk ICC, particularly when features suggest aggressive biology: - large tumor burden - multifocal disease - vascular invasion - suspicious regional nodes --- ### Practice Impact NEO-GAP helped establish the prospective foundation for neoadjuvant and perioperative trials in resectable high-risk ICC.