TY - JOUR
T1 - Efficacy, safety and differential outcomes of immune-chemotherapy with gemcitabine, cisplatin and durvalumab in patients with biliary tract cancers
T2 - A multicenter real world cohort
AU - Mitzlaff, Katharina
AU - Kirstein, Martha M.
AU - Müller, Christian
AU - Venerito, Marino
AU - Olkus, Alexander
AU - Dill, Michael T.
AU - Weinmann, Arndt
AU - Kocheise, Lorenz
AU - Busch, Alina
AU - Schulze, Kornelius
AU - Allo, Gabriel
AU - Waldschmidt, Dirk Thomas
AU - Barsch, Maryam
AU - Bengsch, Bertram
AU - Quante, Michael
AU - Gonzalez-Carmona, Maria A.
AU - Himmelsbach, Vera
AU - Finkelmeier, Fabian
AU - Kloeckner, Roman
AU - Schirmacher, Peter
AU - Marquardt, Jens U.
AU - Zimpel, Carolin
N1 - Publisher Copyright:
© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.
PY - 2024/11
Y1 - 2024/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85204439500&partnerID=8YFLogxK
U2 - 10.1002/ueg2.12656
DO - 10.1002/ueg2.12656
M3 - Journal articles
C2 - 39301763
AN - SCOPUS:85204439500
SN - 2050-6406
VL - 12
SP - 1230
EP - 1242
JO - United European Gastroenterology Journal
JF - United European Gastroenterology Journal
IS - 9
ER -
