Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers: A multicenter real world cohort.

Autor: Mitzlaff K; Department of Medicine I, University Medical Center-Campus Lübeck, Lübeck, Germany., Kirstein MM; Department of Medicine I, University Medical Center-Campus Lübeck, Lübeck, Germany., Müller C; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University Hospital, Magdeburg, Germany., Venerito M; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University Hospital, Magdeburg, Germany., Olkus A; Department of Gastroenterology, Hepatology, Infectious Diseases and Intoxication, Heidelberg University Hospital, Heidelberg, Germany., Dill MT; Department of Gastroenterology, Hepatology, Infectious Diseases and Intoxication, Heidelberg University Hospital, Heidelberg, Germany.; National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.; German Cancer Research Center (DKFZ) Heidelberg, Research Group Experimental Hepatology, Inflammation and Cancer, Heidelberg, Germany., Weinmann A; Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany., Kocheise L; I. Department for Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Busch A; Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schulze K; I. Department for Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Allo G; Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Waldschmidt DT; Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Barsch M; Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, University Medical Center, Freiburg, Germany., Bengsch B; Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, University Medical Center, Freiburg, Germany., Quante M; Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, University Medical Center, Freiburg, Germany., Gonzalez-Carmona MA; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany., Himmelsbach V; Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt, Germany., Finkelmeier F; Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt, Germany., Kloeckner R; Department for Interventional Radiology, University Medical Center-Campus Lübeck, Lübeck, Germany., Schirmacher P; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany., Marquardt JU; Department of Medicine I, University Medical Center-Campus Lübeck, Lübeck, Germany., Zimpel C; Department of Medicine I, University Medical Center-Campus Lübeck, Lübeck, Germany.
Jazyk: angličtina
Zdroj: United European gastroenterology journal [United European Gastroenterol J] 2024 Nov; Vol. 12 (9), pp. 1230-1242. Date of Electronic Publication: 2024 Sep 20.
DOI: 10.1002/ueg2.12656
Abstrakt: Background: Combined Immuno-chemotherapy consisting of gemcitabine, cisplatin and the programmed death-ligand one inhibitor durvalumab (GCD) is the new standard of care for patients with biliary tract cancers (BTC) based on positive results of the TOPAZ-1 study.
Objective: We here evaluated the efficacy and safety of GCD for BTC in a German multicenter real-world patient cohort.
Methods: Patients with BTC treated with GCD from 9 German centers were included. Clinicopathological baseline parameters, overall survival (OS), response rate and adverse events (AEs) were retrospectively analyzed. The prognostic impact was determined by Kaplan-Meier analyses and Cox regression models.
Results: A total of 165 patients treated with GCD between 2021 and 2024 were included in the study. Median OS and median progression-free survival were 14 months (95% CI 10.3-17.7) and 8 months (95% CI 6.8-9.2), respectively. The best overall response rate was 28.5% and disease control rate was 65.5%. While extrahepatic and intrahepatic BTC showed similar outcomes, mOS was significantly shorter in patients with gall bladder cancer (GB-CA) with 9 months (95% CI 5.5-12.4; p = 0.02). In univariate analyses age ≥70 years, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥1, status post cholecystectomy, GB-CA and high baseline CRP values were significantly associated with OS. ECOG PS ≥ 1 and GB-CA remained independent prognostic factors for OS in multivariable cox regression analysis. AEs have been reported in 130 patients (78.8%), including 149 grade 3-4 AEs (25.5%). One patient died of severe infectious pneumonia. Immune-related (ir)AEs occurred in 17 patients (10.3%), including 9 grade 3-4 irAEs (2.2%), which led to treatment interruption in 4 patients.
Conclusions: Immuno-chemotherapy in patients with BTC was feasible, effective and safe in a real-life scenario. Our results were comparable to the phase 3 clinical trial results (TOPAZ-1). Reduced efficacy was noted in patients with GB-CA and/or a reduced performance status that warrants further investigation.
(© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)
Databáze: MEDLINE
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