Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.
Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Eur J Cancer. 2024 Sep;208:114199. doi: 10.1016/j.ejca.2024.114199. Epub 2024 Jun 30.
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.
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).
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.
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.
TOPAZ-1 三期临床试验表明，在晚期胆道癌（BTC）患者中，durvalumab 联合吉西他滨和顺铂可带来生存获益。为了了解该联合方案的真实世界疗效和耐受性，我们对其一线治疗结果进行了全球多中心回顾性分析。
我们纳入了在欧洲、美国和亚洲 11 个国家的 39 个中心接受 durvalumab、吉西他滨和顺铂治疗的不可切除、局部晚期或转移性 BTC 患者。主要终点为总生存期（OS）。
共纳入 666 例患者。中位 OS 为 15.1 个月，中位无进展生存期（PFS）为 8.2 个月。研究者评估的总缓解率为 32.7%，45.2%的患者疾病稳定。基线时 CEA 水平高、ECOG PS＞0、存在转移疾病和 NLR＞3 与较差的生存相关。92.9%的患者发生任何级别的不良事件（AE）（≥2 级：46.6%）。免疫相关 AE（irAE）发生率为 20.0%（≥2 级：2.5%）。3 例死亡（0.5%）被认为与治疗相关，均与免疫治疗无关。常见的 irAE 包括皮疹（所有级别：8.2%；≥2 级：0.3%）、瘙痒（所有级别：10.3%；≥2 级：0.2%）和甲状腺功能减退（所有级别：5.1%；≥2 级：0.3%）。因 AE 而停用 durvalumab 的发生率为 1.5%。对 ESMO 推荐的基因进行了分析，但未发现与结局相关的差异。与单独接受化疗的历史队列患者的比较分析证实了 durvalumab 联合顺铂/吉西他滨对晚期 BTC 患者的生存有积极影响。
这项首次全球真实世界分析在很大程度上证实了 TOPAZ-1 的研究结果，支持吉西他滨、顺铂和 durvalumab 作为晚期 BTC 患者的一线标准治疗。
