Efficacy and safety of first-line chemotherapy in elderly patients with advanced biliary tract cancer: A multi-institutional retrospective study.

548 Background: Systemic chemotherapy is standard treatment for advanced biliary tract cancer (BTC); however, prognosis remains poor. In elderly patients, treatment is often complicated by poor performance status and comorbidities, although clinical evidence is limited. This study evaluated the efficacy and safety of two regimens, gemcitabine/cisplatin plus an immune checkpoint inhibitor (GC+ICI: durvalumab or pembrolizumab) versus gemcitabine/cisplatin/S-1 (GCS), as first-line therapy for elderly patients with advanced BTC. Methods: Elderly patients (aged ≥ 70 years) with histologically confirmed advanced BTC, treated with either GC+ICI or GCS as first-line therapy at seven institutions between April 2019 and January 2025 were enrolled. Overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were assessed. Safety outcomes were evaluated by analyzing the incidence of adverse events (AEs) based on CTCAE v5.0. Subgroup analyses for patients aged ≥75 years were performed to further assess efficacy and safety. Results: A total of 88 elderly patients were enrolled: GC+ICI (n = 61) and GCS (n = 27). Baseline characteristics were generally well-balanced, except for primary tumor type ( p = 0.02) and ERBB2 status ( p = 0.05). The proportion of cases initiating dose reduction was also comparable between the groups ( p = 0.82). In the GC+ICI group, 92% received durvalumab and 8% received pembrolizumab. Median follow-up duration was 13.3 months (mo) for GC+ICI and 6.1 mo for GCS. Efficacy outcomes for GC+ICI and GCS were as follows: ORR 30% vs. 27% ( p = 1.00); DCR 79% vs. 82% ( p = 1.00); median PFS 6.9 mo (95% CI 5.7-7.8) vs. 6.2 mo (95% CI 3.3-9.7) (hazard ratio [HR]: 1.07, 95% CI 0.63-1.83, p = 0.80); median OS 13.3 mo (95% CI 9.2-17.8) vs. 13.0 mo (95% CI 7.7-22.7) (HR: 1.08, 95% CI 0.59-2.00, p = 0.80). The incidence of grade 3-4 AEs was not significantly different between the two groups. In the GC+ICI group, immune-related AEs of any grade included pneumonitis (n = 1), rash (n = 1), thyroid dysfunction (n = 4), adrenal dysfunction (n = 1), hepatitis (n = 1), and colitis (n = 2, one grade 3-4). Among the patients aged ≥75 years, ORR was 42% vs. 13% ( p = 0.21), DCR 79% vs. 63% ( p = 0.38), median PFS 7.4 mo (95% CI 5.4-11.5) vs. 3.2 mo (95% CI 1.2-8.7) (HR: 0.57, 95% CI 0.25-1.30, p = 0.18), and median OS 13.3 mo (95% CI 9.2-17.8) vs. 8.9 mo (95% CI 3.4-not reached) (HR: 0.54, 95% CI 0.22-1.34, p = 0.18). Although not statistically significant, efficacy outcomes tended to favor GC+ICI. AE rates, including immune-related AEs, were comparable in the overall population. Conclusions: No significant differences in efficacy and safety were observed between the GC+ICI and GCS groups in elderly patients with advanced BTC; however, subgroup analyses suggested that patients aged ≥75 years may derive greater benefit from GC+ICI.