Tolerance and response of afatinib combined with tegafur in patients with advanced biliary tract cancer after failure of gemcitabine-based systemic therapy.

BACKGROUND: Off-label afatinib with tegafur was attempted as a last resort option in a patient with advanced gallbladder cancer, achieving satisfactory outcomes. This study evaluated the benefits and toxicity of afatinib with tegafur in advanced biliary tract cancer (BTC). METHODS: This retrospective study included patients who received afatinib combined with tegafur after failure of gemcitabine-based systemic therapy between Oct 2017 and Dec 2024 at the First Affiliated Hospital of Anhui Medical University. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and treatment-related adverse events were evaluated. Cox regression analysis and subgroup analysis were used to assess the relationship between different factors and OS. RESULTS: Fifty-eight patients were included. Two patients achieved partial response, 28 achieved stable disease, and 28 achieved progressive disease, indicating a DCR of 51.7% and an ORR of 3.4%. Median PFS and OS were 4.0 and 6.6 months, respectively. The toxicity associated with afatinib and tegafur was generally acceptable. OS was prolonged in six patients with positive HER-2 and four patients with positive KRAS (G13D) mutations (median: 11.0 months) compared with those without mutations (median: 6.30 months) or unknown genetic status (median: 6.30 months) (P = 0.013). The multivariable Cox analysis showed that no factors were independently associated with OS (all P > 0.05). CONCLUSIONS: Afatinib with tegafur had an acceptable safety profile for advanced BTC after gemcitabine-based systemic therapy failure. The outcome of patients with low performance status and HER-2 or KRAS (G13D) mutations may be better than patients without the mutation.