David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Università degli studi di Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
Lancet. 2023 Oct 7;402(10409):1272-1281. doi: 10.1016/S0140-6736(23)01366-1. Epub 2023 Sep 11.
Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, with few treatment options. NAPOLI 3 aimed to compare the efficacy and safety of NALIRIFOX versus nab-paclitaxel and gemcitabine as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC).
NAPOLI 3 was a randomised, open-label, phase 3 study conducted at 187 community and academic sites in 18 countries worldwide across Europe, North America, South America, Asia, and Australia. Patients with mPDAC and Eastern Cooperative Oncology Group performance status score 0 or 1 were randomly assigned (1:1) to receive NALIRIFOX (liposomal irinotecan 50 mg/m, oxaliplatin 60 mg/m, leucovorin 400 mg/m, and fluorouracil 2400 mg/m, administered sequentially as a continuous intravenous infusion over 46 h) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m and gemcitabine 1000 mg/m, administered intravenously, on days 1, 8, and 15 of a 28-day cycle. Balanced block randomisation was stratified by geographical region, performance status, and liver metastases, managed through an interactive web response system. The primary endpoint was overall survival in the intention-to-treat population, evaluated when at least 543 events were observed across the two treatment groups. Safety was evaluated in all patients who received at least one dose of study treatment. This completed trial is registered with ClinicalTrials.gov, NCT04083235.
Between Feb 19, 2020 and Aug 17, 2021, 770 patients were randomly assigned (NALIRIFOX, 383; nab-paclitaxel-gemcitabine, 387; median follow-up 16·1 months [IQR 13·4-19·1]). Median overall survival was 11·1 months (95% CI 10·0-12·1) with NALIRIFOX versus 9·2 months (8·3-10·6) with nab-paclitaxel-gemcitabine (hazard ratio 0·83; 95% CI 0·70-0·99; p=0·036). Grade 3 or higher treatment-emergent adverse events occurred in 322 (87%) of 370 patients receiving NALIRIFOX and 326 (86%) of 379 patients receiving nab-paclitaxel-gemcitabine; treatment-related deaths occurred in six (2%) patients in the NALIRIFOX group and eight (2%) patients in the nab-paclitaxel-gemcitabine group.
Our findings support use of the NALIRIFOX regimen as a possible reference regimen for first-line treatment of mPDAC.
Ipsen.
For the plain language summary see Supplementary Materials section.
胰腺癌仍然是最致命的恶性肿瘤之一，治疗选择有限。NAPOLI 3 旨在比较 NALIRIFOX 与 nab-紫杉醇和吉西他滨作为转移性胰腺导管腺癌（mPDAC）一线治疗的疗效和安全性。
NAPOLI 3 是一项在全球 18 个国家的 187 个社区和学术地点进行的随机、开放标签、3 期研究，分布在欧洲、北美、南美、亚洲和澳大利亚。患有 mPDAC 和东部合作肿瘤组表现状态评分 0 或 1 的患者按 1:1 随机分配（1:1）接受 NALIRIFOX（脂质体伊立替康 50mg/m、奥沙利铂 60mg/m、亚叶酸 400mg/m 和氟尿嘧啶 2400mg/m，连续静脉输注 46 小时）在 28 天周期的第 1 天和第 15 天或 nab-紫杉醇 125mg/m 和吉西他滨 1000mg/m，在 28 天周期的第 1、8 和 15 天静脉给药。通过交互式网络响应系统，基于地理区域、表现状态和肝转移进行平衡块随机分组。主要终点是在意向治疗人群中的总生存期，在两个治疗组观察到至少 543 个事件时进行评估。在接受至少一剂研究治疗的所有患者中评估安全性。该完成的试验在 ClinicalTrials.gov 上注册，NCT04083235。
2020 年 2 月 19 日至 2021 年 8 月 17 日，770 名患者被随机分配（NALIRIFOX，383；nab-紫杉醇-吉西他滨，387；中位随访 16.1 个月[IQR 13.4-19.1]）。NALIRIFOX 组的中位总生存期为 11.1 个月（95%CI 10.0-12.1），nab-紫杉醇-吉西他滨组为 9.2 个月（8.3-10.6）（风险比 0.83；95%CI 0.70-0.99；p=0.036）。370 名接受 NALIRIFOX 治疗的患者中有 322 名（87%）和 379 名接受 nab-紫杉醇-吉西他滨治疗的患者中有 326 名（86%）发生 3 级或更高的治疗相关不良事件；NALIRIFOX 组有 6 名（2%）患者和 nab-紫杉醇-吉西他滨组有 8 名（2%）患者发生与治疗相关的死亡。
我们的研究结果支持将 NALIRIFOX 方案作为 mPDAC 一线治疗的可能参考方案。
Ipsen。
