Advanced ampullary cancer: post-hoc analysis of the ABC-01, ABC-02, and ABC-03 clinical trials

Ampullary carcinoma (AC) is a rare malignancy. It is often classified within biliary tract cancers (BTC) but lacks dedicated treatment guidelines. This post-hoc analysis evaluated outcomes of patients with advanced AC enrolled in the ABC-01, ABC-02, and ABC-03 clinical trials to provide reference data for future studies. All patients with advanced AC formed the "Descriptive cohort," while those AC treated with cisplatin-gemcitabine (CisGem) comprised the "CisGem-treated cohort." Among 534 trial participants, 28 (5.24%) had AC, and 17 received CisGem. The median age was 63.93 years, and 75.00% were male. Most patients had metastatic disease at baseline (89.29%). Median follow-up for the CisGem-treated cohort was 10.23 months (95% CI 5.98-14.43). The objective response rate was 23.52%, and disease control was achieved in 58.82% of patients. Estimated median progression-free survival (PFS) and overall survival (OS) were 7.98 months (95% CI, 6.86-8.44) and 11.76 months (95% CI, 5.94-14.88), respectively, comparable to outcomes in other BTCs. No reliable prognostic or predictive factors for PFS, OS, or ORR were identified, likely reflecting the small sample size. This analysis underscores the rarity of advanced AC and the challenges in recruiting adequate numbers for dedicated trials. While CisGem remains an appropriate standard-of-care regimen, modest survival outcomes highlight the need for improved therapies. Molecular profiling has revealed potentially actionable alterations, including HER2 amplification and KRAS mutations, supporting precision oncology approaches. This study provides the most comprehensive reference dataset to date for advanced AC treated with CisGem and emphasizes the importance of international collaboration and molecularly guided research to improve outcomes in this rare malignancy.