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@ARTICLE{Mitzlaff:293582,
author = {K. Mitzlaff and M. M. Kirstein and C. Müller and M.
Venerito and A. Olkus and M. T. Dill$^*$ and A. Weinmann and
L. Kocheise and A. Busch and K. Schulze and G. Allo and
D.-T. Waldschmidt and M. Barsch and B. Bengsch and M. Quante
and M. A. Gonzalez-Carmona and V. Himmelsbach and F.
Finkelmeier and R. Kloeckner and P. Schirmacher and J. U.
Marquardt and C. Zimpel},
title = {{E}fficacy, safety and differential outcomes of
immune-chemotherapy with gemcitabine, cisplatin and
durvalumab in patients with biliary tract cancers: {A}
multicenter real world cohort.},
journal = {United european gastroenterology journal},
volume = {12},
number = {9},
issn = {2050-6406},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DKFZ-2024-01905},
pages = {1230-1242},
year = {2024},
note = {2024 Nov;12(9):1230-1242},
abstract = {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.We here evaluated the efficacy and
safety of GCD for BTC in a German multicenter real-world
patient cohort.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.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.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.},
keywords = {biliary tract cancers (Other) / check‐point inhibition
(Other) / cholangiocarcinoma (Other) / cisplatin (Other) /
durvalumab (Other) / gemcitabine (Other) /
immuno‐chemotherapy (Other) / programmed death‐ligand 1
inhibitor (Other)},
cin = {D500},
ddc = {610},
cid = {I:(DE-He78)D500-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39301763},
doi = {10.1002/ueg2.12656},
url = {https://inrepo02.dkfz.de/record/293582},
}