TY - JOUR
T1 - Exploring the impact of durvalumab on biliary tract cancer
T2 - insights from real-world clinical data
AU - Reimann, Patrick
AU - Mavroeidi, Ilektra-Antonia
AU - Burghofer, Jonathan
AU - Taghizadeh, Hossein
AU - Webersinke, Gerald
AU - Kasper, Stefan
AU - Schreil, Georg
AU - Morariu, Darius
AU - Reichinger, Andreas
AU - Baba, Hideo Andreas
AU - Kirchweger, Patrick
AU - Schuler, Martin
AU - Djanani, Angela
AU - Prager, Gerald W
AU - Rumpold, Holger
AU - Benda, Magdalena
AU - Schneider, Eva-Maria
AU - Mink, Sylvia
AU - Winder, Thomas
AU - Doleschal, Bernhard
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/10/3
Y1 - 2024/10/3
N2 - INTRODUCTION: This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the TOPAZ-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes.METHODS: A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies.RESULTS: Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in chromatin remodeling or homologous recombination repair genes were not predictive of survival benefit (HR: 0.45; p = 0.851 and HR: 1.63; p = 0.26, respectively). Patients with molecular-informed second-line therapy showed a trend toward survival benefit (HR: 0.23; p = 0.052).CONCLUSION: This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups.
AB - INTRODUCTION: This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the TOPAZ-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes.METHODS: A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies.RESULTS: Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in chromatin remodeling or homologous recombination repair genes were not predictive of survival benefit (HR: 0.45; p = 0.851 and HR: 1.63; p = 0.26, respectively). Patients with molecular-informed second-line therapy showed a trend toward survival benefit (HR: 0.23; p = 0.052).CONCLUSION: This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups.
KW - Humans
KW - Male
KW - Female
KW - Biliary Tract Neoplasms/drug therapy
KW - Middle Aged
KW - Aged
KW - Retrospective Studies
KW - Antibodies, Monoclonal/therapeutic use
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Adult
KW - Gemcitabine
KW - Deoxycytidine/analogs & derivatives
KW - Aged, 80 and over
UR - http://www.scopus.com/inward/record.url?scp=85205526840&partnerID=8YFLogxK
U2 - 10.1007/s00262-024-03842-y
DO - 10.1007/s00262-024-03842-y
M3 - Journal article
C2 - 39358611
SN - 0340-7004
VL - 73
SP - 251
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 12
M1 - 251
ER -