The real-world clinical effectiveness of durvalumab in advanced biliary tract cancer : A mimic comparative analysis through survival data reconstruction

Hong-Xiang Ji¹Ma-Hui Si²Zhe Sun²Ning Yang^2*zhan chen^1*

• ¹Chenggong Hospital, Xiamen University, Xiamen, China
• ²Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China

Background: The TOPAZ-1 study results represented significant advancement in the treatment of advanced biliary tract cancer (BTC) by combining durvalumab with gemcitabine-cisplatin (DGC). However, the highly selected patient population may not reflect the real-world scenarios. To gain deeper insights into this combination regimen, we conducted an evidence collection and a mimic survival comparative analysis. Methods: Records were identified through a formal search of PubMed and Web of Science. Six retrospective cohort study with real-world evidence were definitively included. The individual patient data for OS and PFS were reconstructed and analyzed. The outcomes different from TOPAZ-1 were summarized and compared. Results: Whether Asia or non-Asia group, the mOS was similar to the TOPAZ-1 (Asian group: 12.57 months vs TOPAZ-1, HR=0.91, 95% CI: 0.69-1.21, logrank P=0.53; non-Asian group: 13.61 months vs TOPAZ-1, HR=1.10, 95% CI: 0.91-1.31, logrank P=0.323). The mPFS for the Asian group did not show significant differences compared to TOPAZ-1 (5.63 months vs TOPAZ-1, HR=1.09, 95% CI: 0.88-1.35, logrank P=0.422), while for the non-Asian group differences exist (6.58 months vs TOPAZ-1, HR=0.80, 95% CI: 0.70-0.92, logrank P=0.002), but potentially influenced by patient ethnicity. The disease control rate in real-world was not so favorable as that in TOPAZ-1. The most common adverse events (AEs) in real-world scenarios were fatigue (26.01%), leukopenia (24.64%), anemia (24.30%), and thrombocytopenia (21.14%). The incidence of immune-related AEs of grades 3-4 was slightly higher in the real world compared to TOPAZ-1 (4.0% vs 2.4%). Factors such as ECOG-PS, age, alternative doses of durvalumab, neutrophil-to-lymphocyte ratio (NLR), baseline CEA levels, baseline CA19-9 levels, and metastatic disease could be prognostic factors under DGC regimen, with NLR showing a potential as a predictive marker for survival benefit. Conclusions: The efficacy and safety of the DGC regimen for patients with advanced BTC are confirmed through a comparative analysis and aggregation of real-world evidence in this study. Further real world investigations are still warranted to determine if the DGC regimen has a broader therapeutic indication and to identify predictive markers for survival benefit. Efforts are required to improve the cost-effectiveness of the DGC regimen to facilitate its wider and standardized use.