含铂化疗联合程序性死亡受体-1 阻断后接受雷莫芦单抗联合多西他赛治疗的晚期非小细胞肺癌的多中心真实世界数据：NEJ051（REACTIVE 研究）。

Multicentre real-world data of ramucirumab plus docetaxel after combined platinum-based chemotherapy with programmed death-1 blockade in advanced non-small cell lung cancer: NEJ051 (REACTIVE study).

机构信息

Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.

Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Hidaka, Japan.

出版信息

Eur J Cancer. 2023 May;184:62-72. doi: 10.1016/j.ejca.2023.01.025. Epub 2023 Feb 11.

BACKGROUND

Ramucirumab plus docetaxel (RD) is a promising treatment for previously treated advanced non-small cell lung cancer (NSCLC). However, its clinical significance after platinum-based chemotherapy plus programmed death-1 (PD-1) blockade remains unclear.

RESEARCH QUESTION

What is the clinical significance of RD as a second-line treatment after the failure of chemo-immunotherapy in NSCLC?

STUDY DESIGN AND METHODS

In this multicentre retrospective study, 288 patients with advanced NSCLC who received RDas second-line therapy after platinum-based chemotherapy plus PD-1 blockade, at 62 Japanese institutions from January 2017 to August 2020, were included. Prognostic analyses were performed using the log-rank test. Prognostic factor analyses were performed using a Cox regression analysis.

RESULTS

A total of 288 patients were enrolled: 222 were men (77.1%), 262 were aged <75 years (91.0%), 237 (82.3%) had smoking history and 269 (93.4%) had a performance status (PS) of 0-1. One hundred ninety-nine patients (69.1%) were classified as adenocarcinoma (AC) and 89 (30.9%) as non-AC. The types of PD-1 blockade used in the first-line treatment were anti-PD-1 antibody and anti-programmed death-ligand 1 antibody in 236 (81.9%) and 52 (18.1%) patients, respectively. The objective response rate for RD was 28.8% (95% confidence interval [CI], 23.7-34.4). The disease control rate was 69.8% (95% CI, 64.1-75.0).The median progression free survival and overall survival were 4.1 months (95% CI, 3.5-4.6) and 11.6 months (95% CI, 9.9-13.9), respectively. In a multivariate analysis, non-AC and PS 2-3 were independent prognostic factors for worse progression free survival , while bone metastasis on diagnosis, PS 2-3 and non-AC were identified as independent prognostic factors for poor overall survival.

INTERPRETATION

RD is a feasible second-line treatment in patients with advanced NSCLC who had received combined chemo-immunotherapy with PD-1 blockade.

CLINICAL TRIAL REGISTRATION NUMBER

UMIN000042333.

背景

雷莫芦单抗联合多西他赛（RD）是一种有前途的治疗方案，适用于先前接受过治疗的晚期非小细胞肺癌（NSCLC）患者。然而，其在铂类化疗联合程序性死亡受体-1（PD-1）阻断后的临床意义尚不清楚。

研究问题

RD 在铂类化疗加 PD-1 阻断失败后作为二线治疗在 NSCLC 中的临床意义是什么？

研究设计与方法

本研究为多中心回顾性研究，共纳入 2017 年 1 月至 2020 年 8 月期间，62 家日本机构的 288 例接受 RD 二线治疗的铂类化疗加 PD-1 阻断后晚期 NSCLC 患者。使用对数秩检验进行预后分析。使用 Cox 回归分析进行预后因素分析。

结果

共纳入 288 例患者：男性 222 例（77.1%），年龄<75 岁 262 例（91.0%），有吸烟史 237 例（82.3%），PS 0-1 级 269 例（93.4%）。199 例（69.1%）为腺癌（AC），89 例（30.9%）为非 AC。一线治疗中使用的 PD-1 阻断剂类型分别为抗 PD-1 抗体和抗程序性死亡配体 1 抗体，分别为 236 例（81.9%）和 52 例（18.1%）。RD 的客观缓解率为 28.8%（95%可信区间[CI]，23.7-34.4）。疾病控制率为 69.8%（95%CI，64.1-75.0）。中位无进展生存期和总生存期分别为 4.1 个月（95%CI，3.5-4.6）和 11.6 个月（95%CI，9.9-13.9）。多因素分析显示，非 AC 和 PS 2-3 是无进展生存期较差的独立预后因素，而诊断时的骨转移、PS 2-3 和非 AC 是总生存期不良的独立预后因素。

结论

RD 是 PD-1 阻断联合化疗后进展的晚期 NSCLC 患者的一种可行的二线治疗选择。

临床试验注册号

UMIN000042333。