TY - JOUR
T1 - Immune-mediated adverse events in the randomized phase 3TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer
AU - Antonuzzo, Lorenzo
AU - Takahashi, Hidenori
AU - Park, Joon Oh
AU - Sookprasert, Aumkhae
AU - Gillmore, Roopinder
AU - Yang, Sheng Shun
AU - Cundom, Juan
AU - Petrova, Mila
AU - Vaccaro, Gina
AU - Holmblad, Marielle
AU - Żotkiewicz, Magdalena
AU - Wang, Julie
AU - Rokutanda, Nana
AU - Oh, Do Youn
N1 - Publisher Copyright:
© The Author(s) 2025. Published by Oxford University Press.
PY - 2025/7/1
Y1 - 2025/7/1
N2 - Introduction: We assessed immune-mediated adverse events (imAEs) in the TOPAZ-1 (NCT03875235) study of durvalumab plus gemcitabine and cisplatin (GemCis) in advanced biliary tract cancer (aBTC). Methods: Participants were randomized 1:1 to durvalumab (1500 mg) or placebo, plus GemCis (gemcitabine [1000 mg/m2] and cisplatin [25 mg/m2]) intravenously, followed by durvalumab (1500 mg) or placebo Q4W. We assessed imAE incidence, time to onset (TTO), and association with overall survival (OS). Results: In durvalumab (n = 338) versus placebo (n = 342), imAEs were reported in 13.9% versus 4.7% of participants, with median TTO of 127.0 versus 86.5 days, respectively. OS HR for durvalumab versus placebo in participants with imAEs was 0.59 (95% CI, 0.30-1.23) and was 0.83 (95% CI, 0.70-1.00) in participants without imAEs. Conclusions: Durvalumab demonstrated an OS benefit versus placebo in aBTC, irrespective of imAEs, which were mostly low grade and manageable. The results in these subgroups were consistent with the overall primary analysis. Trial registration: ClinicalTrials.gov
AB - Introduction: We assessed immune-mediated adverse events (imAEs) in the TOPAZ-1 (NCT03875235) study of durvalumab plus gemcitabine and cisplatin (GemCis) in advanced biliary tract cancer (aBTC). Methods: Participants were randomized 1:1 to durvalumab (1500 mg) or placebo, plus GemCis (gemcitabine [1000 mg/m2] and cisplatin [25 mg/m2]) intravenously, followed by durvalumab (1500 mg) or placebo Q4W. We assessed imAE incidence, time to onset (TTO), and association with overall survival (OS). Results: In durvalumab (n = 338) versus placebo (n = 342), imAEs were reported in 13.9% versus 4.7% of participants, with median TTO of 127.0 versus 86.5 days, respectively. OS HR for durvalumab versus placebo in participants with imAEs was 0.59 (95% CI, 0.30-1.23) and was 0.83 (95% CI, 0.70-1.00) in participants without imAEs. Conclusions: Durvalumab demonstrated an OS benefit versus placebo in aBTC, irrespective of imAEs, which were mostly low grade and manageable. The results in these subgroups were consistent with the overall primary analysis. Trial registration: ClinicalTrials.gov
KW - Biliary tract neoplasms
KW - cholangiocarcinoma
KW - gallbladder neoplasms
KW - immune checkpoint inhibitor
KW - immunotherapy
UR - https://www.scopus.com/pages/publications/105010509677
U2 - 10.1093/oncolo/oyaf148
DO - 10.1093/oncolo/oyaf148
M3 - Article
C2 - 40622010
AN - SCOPUS:105010509677
SN - 1083-7159
VL - 30
JO - Oncologist
JF - Oncologist
IS - 7
M1 - oyaf148
ER -
