Abstract
Introduction
Ampullary adenocarcinoma (AC) is a rare malignancy with limited evidence to guide systemic treatment in the metastatic setting.Methods
This post hoc analysis was conducted within the French national prospective FFCD-AC cohort, which enrolled patients undergoing curative-intent resection for localized AC. Patients who developed metastatic recurrence and received at least one line of systemic chemotherapy were included. Overall survival (OS) and progression-free survival (PFS) were calculated from first-line treatment initiation. Prognostic factors were assessed using Cox proportional hazards models.Results
A total of 85 patients were included. The most frequent histological subtype was the biliopancreatic subtype (43/85, 50.6%). First-line therapy consisted of a 5FU-based regimen in 64.7% of patients and a gemcitabine-based regimen in 35.3%. Objective response rate (ORR) and disease control rate (DCR) were similar between regimens (ORR: 36.2% vs 32.0%, p = 0.73; DCR: 72.3% vs 68.0%, respectively p = 0.78). After a median follow-up of 65.4 months, median PFS and OS were 6.7 months (95%CI, 4.8-8.9) and 15.6 months (95% CI, 11.9-18.2), respectively. In multivariable analysis, longer PFS was associated with 5FU-based therapy (HR 0.53, 95% CI 0.32-0.88; p = 0.01), one metastatic site, and bi- or triplet regimens, whereas absence of liver metastases was the only factor associated with improved OS (HR 0.58, 95% CI 0.34-0.97; p = 0.04). Histological subtype was not independently associated with outcomes.Conclusion
In this real-world cohort of metastatic AC, 5FU-based first-line chemotherapy improved PFS but not OS compared with gemcitabine-based regimens. The absence of liver metastases was the only independent prognostic factor for OS, and no statistically significant association between histological subtype and survival was demonstrated. Prospective studies integrating molecular stratification are now needed.