PD-8 Outcomes by disease status in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study

TOPAZ-1 (NCT03875235) was a randomised, double-blind, global, phase 3 study evaluating the efficacy and safety of durvalumab plus gemcitabine and cisplatin (durvalumab) as first-line treatment for patients with advanced biliary tract cancer (BTC; Oh D-Y, et al. J Clin Oncol 2022;40[suppl 4]. Abs 378). Durvalumab significantly improved overall survival (OS) versus placebo plus gemcitabine and cisplatin (placebo) and represents a potential new treatment option for patients with advanced BTC. In BTC, disease status at baseline (initially unresectable vs recurrent [>6 months after surgery with curative intent or >6 months after adjuvant therapy]) may impact response to treatment. The aim of this exploratory subgroup analysis of TOPAZ-1 was to assess efficacy outcomes by disease status at baseline in patients receiving durvalumab versus placebo. Patients with BTC were randomised 1:1 to receive durvalumab (1500 mg) or placebo on Day 1 Q3W, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) on Day 1 and 8 Q3W, for up to 8 cycles, followed by durvalumab or placebo monotherapy until disease progression, unacceptable toxicity or other discontinuation criteria were met. Randomisation was stratified by disease status and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Subgroup analysis of OS, progression-free survival (PFS), objective response rate (ORR) and duration of response (DoR) per RECIST v1.1 by disease status at baseline (initially unresectable or recurrent) was performed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for OS and PFS using a Cox proportional hazards model, and odds ratios (ORs) and 95% CIs for ORR were calculated using the Cochran-Mantel Haenszel test. The study included more patients with initially unresectable than recurrent disease (durvalumab, n=274 [80.4%] vs n=67 [19.6%]; placebo, n=279 [81.1%] vs n=64 [18.6%]). HRs for OS favoured durvalumab for both initially unresectable (0.84; 95% CI, 0.69–1.03) and recurrent (0.56; 95% CI, 0.32–0.96) disease; HRs for PFS also favoured durvalumab in both subgroups (0.79; 95% CI 0.66–0.95 and 0.63; 95% CI 0.42–0.94, respectively). ORs for ORR favoured durvalumab for both initially unresectable (1.61; 95% CI, 1.06–2.45) and recurrent (1.52; 95% CI 0.73–3.18) disease. Median DoR for durvalumab versus placebo was 6.0 versus 5.1 months for initially unresectable, and 9.7 versus 7.9 months for recurrent disease. Percentage of responders with a DoR of at least 9 and 12 months was numerically higher with durvalumab versus placebo for both initially unresectable (9-month, 21.5% vs 20.3%; 12-month, 16.7% vs 10.7%) and recurrent (9 months, 58.8% vs 38.1%; 12 months, 48.1% vs 25.4%) disease. In TOPAZ-1, addition of durvalumab to GemCis improved efficacy outcomes both in patients with initially unresectable and patients with recurrent disease at baseline, though the relative benefit versus placebo appears greater for recurrent compared with initially unresectable disease. These findings support the use of durvalumab plus GemCis as a potential new treatment option for patients with advanced BTC, irrespective of disease status.