Supplementary Material for: Final results from RIBBIT: A randomized phase III study to evaluate efficacy and quality of life in patients with metastatic hormone receptor-positive HER2-negative breast cancer receiving ribociclib in combination with endocrine therapy or chemotherapy with or without bevacizumab in the first-line setting

Background
We investigated the efficacy and health-related quality of life (HRQoL) in patients receiving either ribociclib plus endocrine therapy (ET) or chemotherapy with/without bevacizumab as first-line treatment of metastatic HR-positive, HER2-negative breast cancer (BC).
Patients and Methods
In this randomized, phase III study (RIBBIT), 38 patients diagnosed with metastatic HR-positive, HER2-negative BC with presence of visceral metastases recruited between May 2018 and December 2020 were randomly assigned in a 1:1 ratio to either arm A (ribociclib+ET) or arm B (chemotherapy with/without bevacizumab) at 12 sites in Germany. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS), patient-reported HRQoL, and frequency and type of adverse events. During study conduction, the recruitment rate was persistently and considerably lower than originally expected. Therefore, the recruitment was ended prematurely. The study was initially designed to enroll and randomize 158 patients.
Results
Median [95% CI] PFS was 27.3 months [19.1 – NA, parameter not estimable] in arm A and 15.8 months [8.2 – NA] in arm B. Complete responses were achieved only in arm A (n=2, 10.5%). The ORR [95% CI] between arm A (57.9% [33.5-79.7]) and arm B (52.6% [28.9-75.6]) was comparable. Median OS [95% CI] was not reached in arm A, while in arm B median OS was 28.4 months [25.0 – NA]. Patients in arm A reported less burden by side-effects. No new safety signals emerged.
Conclusion
Treatment of patients with visceral metastatic HR-positive, HER2-negative BC with ribociclib in combination with ET showed a tendency towards a more favorable clinical outcome. Despite small numbers of patients and sites, this head-to-head comparison with chemotherapy supports the use of ribociclib with ET in patients with visceral metastasis at risk of fast disease progression.

The RIBBIT study was registered at ClinicalTrials.gov (EudraCT No: 2017-002930-22), 14/02/2018.

研究背景
本研究旨在评估接受瑞博西尼（ribociclib）联合内分泌治疗（endocrine therapy, ET），或联合/不联合贝伐珠单抗（bevacizumab）的化疗作为一线方案治疗激素受体阳性、人表皮生长因子受体2阴性转移性乳腺癌（HR-positive, HER2-negative breast cancer, 以下简称乳腺癌（BC））患者时的疗效与健康相关生活质量（health-related quality of life, HRQoL）。

患者与方法
本研究为一项随机化Ⅲ期临床试验（RIBBIT），于2018年5月至2020年12月间在德国12家研究中心开展。共纳入38例经确诊的伴内脏转移的激素受体阳性、人表皮生长因子受体2阴性转移性乳腺癌患者，按1:1比例随机分配至A组（瑞博西尼联合内分泌治疗）或B组（联合/不联合贝伐珠单抗的化疗）。本研究的主要终点为无进展生存期（progression-free survival, PFS），次要终点包括客观缓解率（overall response rate, ORR）、总生存期（overall survival, OS）、患者报告的健康相关生活质量，以及不良事件的发生频率与类型。
研究实施期间，入组率持续显著低于初始预期，因此提前终止了入组。本研究最初计划纳入并随机分配158例患者。

研究结果
A组患者的中位无进展生存期[95%置信区间（confidence interval, CI）]为27.3个月[19.1–未获取，参数无法估算]，B组为15.8个月[8.2–未获取]。仅A组患者获得完全缓解（n=2，占比10.5%）。A组与B组的客观缓解率[95%置信区间]分别为57.9%[33.5-79.7]与52.6%[28.9-75.6]，组间无显著差异。A组患者的中位总生存期未达到[95%置信区间]，而B组中位总生存期为28.4个月[25.0–未获取]。A组患者报告的不良反应负担更轻，未观察到新的安全性信号。

研究结论
针对伴内脏转移的激素受体阳性、人表皮生长因子受体2阴性转移性乳腺癌患者，采用瑞博西尼联合内分泌治疗的方案展现出更优的临床结局趋势。尽管本研究的患者与研究中心数量有限，但这项与化疗的头对头比较仍支持，对于存在疾病快速进展风险的内脏转移性乳腺癌患者，可采用瑞博西尼联合内分泌治疗方案。

本RIBBIT研究于2018年2月14日在ClinicalTrials.gov注册（EudraCT编号：2017-002930-22）。