A multicenter, prospective observational study of chemotherapy in elderly patients with biliary tract cancer.

567 Background: In addition to gemcitabine (GEM) plus cisplatin (GC), GEM plus S-1 (GS) and GC plus S-1 (GCS) have been used as standard treatments for advanced biliary tract cancer (aBTC) based on results from phase III trials in Japan prior to the introduction of immune checkpoint inhibitors. The aim of this study was to evaluate the efficacy and safety of these chemotherapies in elderly patients (pts) with aBTC. Methods: This was a multicenter, prospective observational study (UMIN000045156). Inclusion criteria were: age >=70 years; unresectable or recurrent BTC; and scheduled for chemotherapy with GCS, GC, GS, GEM, or S-1. Data were prospectively collected on treatment tolerability, safety and geriatric assessments (G8, IADL, CCI), and overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were evaluated. Inverse probability-weighted propensity score analyses were performed for comparisons of GCS versus GC and of GC versus GEM. Results: A total of 305 pts were enrolled from 53 Japanese hospitals between August 2021 and January 2023. Of these, 294 received chemotherapy (GCS, n=75; GC, n=131; GS, n=26; GEM, n=52; S-1, n=10). Median follow-up was 11.8 months for all pts. Median age was 76 years (range: 70-89 years). Adverse events are summarized in the Table 1. Rates of pts without G8 deterioration after 3 months were 58.7% for GCS, 55.7% for GC, 34.6% for GS, 42.3% for GEM, and 20% for S-1. Rates of pts without IADL deterioration after 3 months were 82.7% for GCS, 73.3% for GC, 42.3% for GS, 57.7% for GEM, and 40.0% for S-1. With inverse probability-weighted propensity score analyses, median OS was 16.4 months (95% confidence interval [CI], 14.7–20.6 months) in the GCS group and 13.3 months (95%CI, 11.7–21.9 months) in the GC group (hazard ratio [HR] 0.80, 95%CI 0.55–1.17; p=0.258). Median PFS was 11.8 months (95%CI, 9.7–14.5 months) in the GCS group and 7.7 months (95%CI, 6.0–10.2 months) in the GC group (HR 0.55, 95%CI 0.38–0.80; p=0.002). ORR was 31.0% in the GCS group and 15.5% in the GC group (p<0.001). Median OS was 13.3 months (95%CI 11.1–19.4 months) in the GC group and 15.5 months (95%CI 6.4–18.7 months) in the GEM group (HR 0.74, 95%CI 0.42–1.29; p=0.282). Median PFS was 6.9 months (95%CI 6.0–9.6 months) in the GC group and 5.1 months (95%CI 3.0–12.0 months) in the GEM group (HR 0.79, 95%CI 0.42–1.49; p=0.463). ORR was 14.1% in the GC group and 7.5% in the GEM group (p=0.305). Conclusions: GCS is an effective therapy compared to GC in elderly pts with aBTC without increasing toxicities or deteriorating activities of daily living. Clinical trial information: UMIN000045156. Chemotherapy-related adverse events (grade 3 and 4). Events, n (%) GCS(n=75) GC(n=131) GS(n=26) GEM(n=52) S-1(n=10) Neutropenia 20 (26.7) 54 (41.2) 8 (30.8) 10 (19.2) 0 Thrombocytopenia 8 (10.7) 9 (6.9) 2 (7.7) 1 (1.9) 0 Anorexia 2 (2.7) 6 (4.6) 2 (7.7) 3 (5.8) 3 (30.0) Malaise 0 8 (6.1) 4 (15.4) 4 (7.7) 3 (30.0) Febrile neutropenia 1 (1.3) 1 (0.8) 2 (7.7) 1 (1.9) 0