Durvalumab plus gemcitabine-cisplatin versus S-1 plus gemcitabine-cisplatin in advanced biliary tract cancer: a comparative study

Following the TOPAZ-1 trial, chemoimmunotherapy with durvalumab plus gemcitabine and cisplatin (GCD) became the standard first-line treatment of advanced biliary tract cancer (BTC). This study aimed to compare the therapeutic efficacy of GCD and gemcitabine, cisplatin, and S-1 (GCS). This single-center, retrospective study consecutively included patients with advanced BTC receiving primary treatment with GCD or GCS between November 2018 and August 2024. A total 265 patients with advanced BTC were included: 97 were treated with GCD and 168 were treated with GCS. Median overall survival (OS) was 17.1 months [95% confidence interval (CI) 12.7-20.6 months] in the GCD group versus 18.3 months (95% CI 15.4-20.4 months) in the GCS group, with no statistically significant difference ( P = 0.509). Median progression-free survival (PFS) was 8.0 months (95% CI 5.9-9.6 months) in the GCD group versus 8.9 months (95% CI 7.1-11.4 months) in the GCS group ( P = 0.077). No differences were noted in objective response rates, whereas median duration of response (DoR) was significantly longer in the GCS group (12.7 months) than that in the GCD group (7.5 months) ( P = 0.022). Patients with ARID1A or PIK3CA alterations, or with SMAD4 wild-type, had better OS with GCS than with GCD. GCD and GCS provide comparable survival outcomes and safety in clinical practice, with a significantly longer DoR in the GCS group. Alongside GCD, GCS represents one of the standard treatment options for advanced BTC. • We compared the efficacies of GCD and gemcitabine, cisplatin, and S-1 (GCS). • GCD and GCS provide comparable survival outcomes and safety in clinical practice. • Patients with ARID1A or PIK3CA alterations, or with SMAD4 wild-type, had better OS with GCS. • GCS represents one of the standard treatment options for advanced BTC.