# Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B)

## TL;DR

This study compares chemotherapy regimens for older patients with advanced biliary tract cancer, focusing on survival and safety outcomes.

## Contribution

The study evaluates the efficacy and safety of combination chemotherapy in older patients with biliary tract cancer using propensity-score matched analysis.

## Key findings

- GEM + CDDP + S-1 showed longer progression-free survival than GEM + CDDP without additional toxicity.
- GEM + CDDP and gemcitabine had similar overall survival outcomes for vulnerable older patients.
- Safety profiles of GEM + CDDP and GEM + CDDP + S-1 were comparable, but both were more toxic than gemcitabine alone.

## Abstract

Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.

This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.

This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55–1.17) and 0.55 for PFS (95% CI 0.38–0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42–1.29) and 0.79 for PFS (95% CI 0.42–1.49).

GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC.

The online version contains supplementary material available at 10.1007/s00535-025-02294-0.