度伐利尤单抗联合吉西他滨和顺铂用于晚期胆管癌的随机3期TOPAZ-1研究中的免疫介导不良事件。
Immune-mediated adverse events in the randomized phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer.
作者信息
Antonuzzo Lorenzo, Takahashi Hidenori, Park Joon Oh, Sookprasert Aumkhae, Gillmore Roopinder, Yang Sheng-Shun, Cundom Juan, Petrova Mila, Vaccaro Gina, Holmblad Marielle, Żotkiewicz Magdalena, Wang Julie, Rokutanda Nana, Oh Do-Youn
机构信息
Clinical Oncology Unit, Careggi University Hospital, and Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.
Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567, Japan.
出版信息
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyaf148.
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 NCT03875235.
引言
我们在一项关于度伐利尤单抗联合吉西他滨和顺铂（GemCis）治疗晚期胆管癌（aBTC）的TOPAZ-1（NCT03875235）研究中评估了免疫介导的不良事件（imAE）。
方法
参与者按1:1随机分为度伐利尤单抗组（1500 mg）或安慰剂组，联合静脉注射GemCis（吉西他滨[1000 mg/m²]和顺铂[25 mg/m²]），随后度伐利尤单抗组（1500 mg）或安慰剂组每4周一次。我们评估了imAE的发生率、发病时间（TTO）以及与总生存期（OS）的关联。
结果
在度伐利尤单抗组（n = 338）与安慰剂组（n = 342）中，分别有13.9%和4.7%的参与者报告了imAE，中位TTO分别为127.0天和86.5天。发生imAE的参与者中，度伐利尤单抗组与安慰剂组的OS风险比为0.59（95%CI，0.30 - 1.23），未发生imAE的参与者中该风险比为0.83（95%CI，0.70 - 1.00）。
结论
在aBTC中，度伐利尤单抗相对于安慰剂显示出OS获益，无论imAE情况如何，imAE大多为低级别且可控。这些亚组的结果与总体初步分析一致。
试验注册
ClinicalTrials.gov NCT03875235。
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