Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer.
Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer.
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DOI：
10.1056/evidoa2200015
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发表时间：
2022-08-01
期刊：
影响因子：
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通讯作者：
Valle, Juan W
中科院分区：
文献类型：
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作者：
Oh, Do-Youn;Ruth He, Aiwu;Valle, Juan W
背景技术背景：晚期胆道癌患者预后差，一线标准治疗（吉西他滨加顺铂）10多年来一直保持不变。黄玉-1试验评估了durvalumab联合化疗治疗晚期胆道癌患者的效果。方法：在这项双盲、安慰剂对照、III期研究中，我们将既往未经治疗的不可切除或转移性胆道癌患者或复发性疾病患者以1：1的比例随机分配，接受durvalumab或安慰剂联合吉西他滨+顺铂治疗，最多8个周期，随后接受durvalumab或安慰剂单药治疗，直至疾病进展或出现不可接受的毒性。主要目的是评估总生存期。次要终点包括无进展生存期、客观缓解率和安全性。结果：总体而言，685例患者被随机分配到durvalumab（n=341）或安慰剂（n=344）与化疗。截至数据截止日期，durvalumab组有198例患者（58.1%）死亡，安慰剂组有226例患者（65.7%）死亡。总生存期的风险比为0.80（95%置信区间[CI]，0.66 - 0.97; P=0.021）。估计的24个月总生存率为24.9%（95% CI，17.9 - 32.5），安慰剂为10.4%（95% CI，4.7 - 18.8）。无进展生存期的风险比为0.75（95% CI，0.63 - 0.89; P=0.001）。durvalumab组的客观缓解率为26.7%，安慰剂组为18.7%。durvalumab和安慰剂组3级或4级不良事件的发生率分别为75.7%和77.8%。结论：Durvalumab+化疗与安慰剂+化疗相比显著改善了总生存期，并且在预定的次要终点（包括无进展生存期和客观缓解率）方面显示出与安慰剂+化疗相比的改善。两个治疗组的安全性特征相似。（由阿斯利康资助; ClinicalTrials.gov编号，NCT 03875235。）
BACKGROUND: Patients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years. The TOPAZ-1 trial evaluated durvalumab plus chemotherapy for patients with advanced biliary tract cancer. METHODS: In this double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with previously untreated unresectable or metastatic biliary tract cancer or with recurrent disease 1:1 to receive durvalumab or placebo in combination with gemcitabine plus cisplatin for up to eight cycles, followed by durvalumab or placebo monotherapy until disease progression or unacceptable toxicity. The primary objective was to assess overall survival. Secondary end points included progression-free survival, objective response rate, and safety. RESULTS: Overall, 685 patients were randomly assigned to durvalumab (n=341) or placebo (n=344) with chemotherapy. As of data cutoff, 198 patients (58.1%) in the durvalumab group and 226 patients (65.7%) in the placebo group had died. The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66 to 0.97; P=0.021). The estimated 24-month overall survival rate was 24.9% (95% CI, 17.9 to 32.5) for durvalumab and 10.4% (95% CI, 4.7 to 18.8) for placebo. The hazard ratio for progression-free survival was 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates were 26.7% with durvalumab and 18.7% with placebo. The incidences of grade 3 or 4 adverse events were 75.7% and 77.8% with durvalumab and placebo, respectively. CONCLUSIONS: Durvalumab plus chemotherapy significantly improved overall survival versus placebo plus chemotherapy and showed improvements versus placebo plus chemotherapy in prespecified secondary end points including progression-free survival and objective response rate. The safety profiles of the two treatment groups were similar. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03875235.)