Potentially prognostic factors of overall survival in advanced biliary tract cancer in the randomised phase III TOPAZ-1 study

초록

Background In TOPAZ-1 (NCT03875235), durvalumab (D) + gemcitabine and cisplatin (GC) improved overall survival (OS) vs placebo (PBO) + GC in participants with advanced biliary tract cancer (aBTC; primary analysis: hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66–0.97, p=0.021 [significance threshold p=0.03]) and after a further 6.5 months of follow-up (HR 0.76, 95% CI 0.64–0.91). This exploratory analysis assessed baseline clinical factors for potential prognostic (associated with OS) or predictive (of OS benefit with D + GC) value in TOPAZ-1. Methods Potentially prognostic factors were evaluated using Cox proportional hazards models with treatment and each factor. An exploratory adjusted HR for D + GC vs PBO + GC was estimated with a model adjusting for prognostic factors identified by stepwise selection. Unstratified Cox proportional hazards models and interaction tests were performed to assess potential predictive factors. Data cut-off was 25 February 2022. Results Potentially prognostic clinical factors are shown (Table). The HR for D + GC vs PBO + GC, adjusted for disease status, primary tumour location, sex, PD-L1, neutrophil to lymphocyte ratio (NLR), cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), liver metastasis, liver involvement (locally advanced or metastatic site in liver/gallbladder), body weight, LDH, albumin and total bilirubin, was 0.70 (95% CI 0.59–0.84). OS HRs for D + GC vs PBO + GC were <1 across assessed clinical (Table) and laboratory factors; no predictive factors for D + GC were found. Conclusions Benefit with D + GC was consistent across assessed factors and stable after adjusting for potentially prognostic factors, supporting D + GC as first-line treatment for aBTC.