艾瑞布林对比S-1作为一线或二线化疗评估HER2阴性转移性乳腺癌患者健康相关生活质量和总生存期（RESQ研究）：一项非劣效性、随机、对照、开放标签的3期试验

Eribulin versus S-1 as first or second-line chemotherapy to assess health-related quality of life and overall survival in HER2-negative metastatic breast cancer (RESQ study): a non-inferiority, randomised, controlled, open-label, phase 3 trial.

作者信息

Takahashi Masato, Kikawa Yuichiro, Kashiwabara Kosuke, Taira Naruto, Iwatani Tsuguo, Shimozuma Kojiro, Ohtani Shoichiro, Yoshinami Tetsuhiro, Watanabe Junichiro, Kashiwaba Masahiro, Watanabe Ken-Ichi, Kitada Masahiro, Sakaguchi Koichi, Tanabe Yuko, Aihara Tomohiko, Mukai Hirofumi

机构信息

Hokkaido University Hospital, Sapporo, Japan.

Kansai Medical University Hospital, Osaka, Japan.

出版信息

EClinicalMedicine. 2024 Jul 16;74:102715. doi: 10.1016/j.eclinm.2024.102715. eCollection 2024 Aug.

BACKGROUND

Eribulin prolongs overall survival (OS) of patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), particularly in later chemotherapy (ChT) treatment. However, the health-related quality of life (HRQoL) and efficacy of first or second-line therapy in eribulin-treated patients remain unknown. Using eribulin in the first- or second-line may demonstrate the non-inferiority of HRQoL compared to S-1, an oral 5-fluorouracil derivative, while maintaining OS.

METHODS

This randomised, controlled, open-label, phase III trial was conducted at 50 hospitals in Japan. Patients were enrolled from June 2016 and October 2019. Patients with HER2-negative MBC once under or no previous ChT were randomly assigned (1:1) to receive eribulin or S-1. HRQoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) every six weeks until week 24 and every nine weeks until week 42. The primary endpoint was the deterioration defined as more than 10 points worsening of the general health score of QLQ-C30 or death within one year after randomisation. The secondary endpoints included OS. (Trial ID: UMIN000021398).

FINDINGS

Three hundred and two patients were enrolled, with 152 and 148 assigned to the eribulin and S-1 groups, respectively. The questionnaire compliance rate was 85.6%. Risk difference of global health status deterioration through one year was -0.66% (95% CI: -12.47-11.16; non-inferiority P = 0.077) for eribulin compared to S-1 groups. Median time to first deterioration for global health status score was 5.64 (95% CI: 3.51-8.00) and 5.28 months (95% CI: 3.28-7.80) in the eribulin and S-1 groups, respectively. The median OS was 34.7 and 27.8 months, (HR: 0.72, 95% CI: 0.54-0.96; P = 0.026); the median progression-free survival was 7.57 and 6.75 months in the eribulin and S-1 groups, (HR: 0.88, 95% CI: 0.67-1.16; P = 0.35), respectively. No new adverse events occurred.

INTERPRETATION

The time of the first clinical deterioration was similar between the two groups and OS significantly increased in eribulin-treated patients.

FUNDING

This study was funded by CSPOR-BC and Eisai CO., Ltd.

背景

艾日布林可延长人表皮生长因子受体2（HER2）阴性转移性乳腺癌（MBC）患者的总生存期（OS），尤其是在晚期化疗（ChT）治疗中。然而，艾日布林治疗患者的健康相关生活质量（HRQoL）和一线或二线治疗的疗效仍不明确。在一线或二线使用艾日布林可能显示出与口服5-氟尿嘧啶衍生物S-1相比，HRQoL不劣，同时维持OS。

方法

这项随机、对照、开放标签的III期试验在日本的50家医院进行。患者于2016年6月至2019年10月入组。既往接受过或未接受过ChT的HER2阴性MBC患者被随机分配（1:1）接受艾日布林或S-1治疗。使用欧洲癌症研究与治疗组织（EORTC）生活质量问卷核心30（QLQ-C30）每六周评估一次HRQoL，直至第24周，之后每九周评估一次，直至第42周。主要终点是定义为QLQ-C30总体健康评分恶化超过10分或随机分组后一年内死亡的病情恶化。次要终点包括OS。（试验编号：UMIN000021398）

结果

共纳入302例患者，分别有152例和148例被分配至艾日布林组和S-1组。问卷依从率为85.6%。与S-1组相比，艾日布林组一年中总体健康状况恶化的风险差异为-0.66%（95%CI：-12.47-11.16；非劣效性P=0.077）。艾日布林组和S-1组总体健康状况评分首次恶化的中位时间分别为5.64（95%CI：3.51-8.00）和5.28个月（95%CI：3.28-7.80）。中位OS分别为34.7个月和27.8个月，（HR：0.72，95%CI：0.54-0.96；P=0.026）；艾日布林组和S-1组的中位无进展生存期分别为7.57个月和6.75个月，（HR：0.88，95%CI：0.67-1.16；P=0.35）。未出现新的不良事件。