NAPOLI-1 期研究：脂质体伊立替康治疗转移性胰腺癌：最终总生存分析和长期生存者特征。

NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors.

机构信息

Washington University School of Medicine, 660 S Euclid Avenue, St. Louis, MO 63110, USA.

The Christie NHS Foundation Trust, 550 Wilmslow Rd., Manchester, M20 4BX, UK.

出版信息

Eur J Cancer. 2019 Feb;108:78-87. doi: 10.1016/j.ejca.2018.12.007. Epub 2019 Jan 14.

DOI:10.1016/j.ejca.2018.12.007

PMID:30654298

Abstract

BACKGROUND

Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial.

PATIENTS AND METHODS

Patients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) for the first 4 weeks of 6-week cycles. Baseline characteristics and efficacy in the overall population were compared with those in patients who survived ≥1 year. Through 16th November 2015, 382 overall survival events had occurred.

RESULTS

The overall survival advantage for nal-IRI+5-FU/LV vs 5-FU/LV was maintained from the original nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1) analysis (6.2 vs 4.2 months, respectively; HR, 0.75; 95% confidence interval: 0.57-0.99). Median progression-free survival, objective response rate and disease control rate also favoured nal-IRI+5-FU/LV therapy. Estimated one-year overall survival rates were 26% with nal-IRI+5-FU/LV and 16% with 5-FU/LV. Baseline characteristics associated with long-term survival in the nal-IRI+5-FU/LV arm were Karnofsky performance status ≥90, age ≤65 years, lower CA19-9 levels, neutrophil-to-lymphocyte ratio ≤5 and no liver metastases. No new safety concerns were detected.

CONCLUSIONS

The survival benefits of nal-IRI+5-FU/LV versus 5-FU/LV were maintained over an extended follow-up, and prognostic markers of survival ≥1 year were identified.

CLINICAL TRIAL REGISTRATION NUMBER

NCT01494506.

摘要

背景

对于已接受吉西他滨为基础的治疗的转移性胰腺导管腺癌（mPDAC）患者，脂质体伊立替康（nal-IRI）联合 5-氟尿嘧啶和亚叶酸（5-FU/LV）被批准用于治疗。这一批准是基于全球 III 期 NAPOLI-1 试验中 nal-IRI+5-FU/LV 与单独 5-FU/LV 相比显著提高了中位总生存期（6.1 个月 vs 4.2 个月；风险比 [HR]，0.67）。在此，我们报告了 NAPOLI-1 试验中的最终生存分析和与长期生存（≥1 年）相关的基线特征。

方法

mPDAC 患者按 1:1:1 随机分配接受 nal-IRI+5-FU/LV（n=117）、nal-IRI（n=151）或 5-FU/LV（n=149）治疗，每 6 周治疗 4 周。比较总体人群的基线特征和疗效与≥1 年存活的患者。截至 2015 年 11 月 16 日，共发生 382 例总生存事件。

结果

nal-IRI+5-FU/LV 与 5-FU/LV 的总生存优势从之前基于吉西他滨的治疗的原始纳米脂质体伊立替康联合氟尿嘧啶和亚叶酸治疗转移性胰腺癌（NAPOLI-1）分析中得到维持（分别为 6.2 个月和 4.2 个月；HR，0.75；95%置信区间：0.57-0.99）。无进展生存期、客观缓解率和疾病控制率也有利于 nal-IRI+5-FU/LV 治疗。估计 nal-IRI+5-FU/LV 的 1 年总生存率为 26%，5-FU/LV 为 16%。nal-IRI+5-FU/LV 臂中与长期生存相关的基线特征包括 Karnofsky 表现状态≥90、年龄≤65 岁、较低的 CA19-9 水平、中性粒细胞与淋巴细胞比值≤5 和无肝转移。未发现新的安全问题。