背景:TOPAZ-1III期试验显示,Durvalumab联合吉西他滨和顺铂对晚期胆道癌(BTC)患者的生存获益。要了解这种组合的真实世界功效和耐受性,我们对其一线治疗结局进行了全球多中心回顾性分析.
方法:我们纳入了不可切除的患者,本地先进,或转移性BTC用Durvalumab治疗,吉西他滨,和顺铂在11个国家的39个地点(欧洲,美国,和亚洲)。主要终点是总生存期(OS)。
结果:纳入666例患者。中位OS为15.1个月,中位PFS为8.2个月。研究者评估的总反应率为32.7%,45.2%的患者病情稳定。高基线CEA水平,ECOGPS>0,转移性疾病,NLR>3与生存率低相关。任何级别的不良事件(AE)发生在92.9%的患者中(>2级:46.6%)。免疫相关不良事件(irAEs)发生率为20.0%(等级>2:2.5%)。3例死亡(0.5%)被认为与治疗有关,与免疫疗法无关。常见的iRAAE为皮疹(8.2%所有等级;0.3%等级>2),瘙痒(10.3%所有等级;0.2%等级>2),和甲状腺功能减退症(所有等级为5.1%;0.3%等级>2)。Durvalumab因不良事件停药率为1.5%。分析了ESMO推荐的基因,没有发现结果差异。与仅接受化疗的历史队列患者的比较分析证实了durvalumab联合顺铂/吉西他滨对生存的积极影响。
结论:首次全球现实世界分析在很大程度上证实了TOPAZ-1的发现,支持吉西他滨,顺铂,和durvalumab作为晚期BTC患者的一线治疗标准。
BACKGROUND: The TOPAZ-1 phase III trial showed a survival benefit with
durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination\'s real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes.
METHODS: We included patients with unresectable, locally advanced, or metastatic BTC treated with
durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS).
RESULTS: 666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2).
Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of
durvalumab in combination with cisplatin/gemcitabine.
CONCLUSIONS: This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and
durvalumab as a first-line standard of care for patients with advanced BTC.