Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3
Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3
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DOI：
10.1200/jco.2018.78.9909
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发表时间：
2018-08-20
影响因子：
45.3
通讯作者：
Jerusalem, Guy
中科院分区：
文献类型：
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作者：
Slamon, Dennis J.;Neven, Patrick;Jerusalem, Guy
PurposeThis III期研究评价了ribociclib加氟维司群在激素受体阳性/人表皮生长因子受体2阴性晚期乳腺癌患者中的作用，这些患者是初治或在晚期setting.Patients和MethodsPatients中接受了多达一线的内分泌治疗，以2：1的比例随机分配至ribociclib加氟维司群或安慰剂加氟维司群。主要终点是当地评估的无进展生存期。次要终点包括总生存率、总缓解率和safety.ResultsA共484例绝经后妇女被随机分配至ribociclib+氟维司群组，242例被分配至安慰剂+氟维司群组。与安慰剂+氟维司群相比，ribociclib+氟维司群的中位无进展生存期显著改善：分别为20.5个月（95% CI，18.5 - 23.5个月）和12.8个月（95% CI，10.9 - 16.3个月）（风险比，0.593; 95% CI，0.480 - 0.732; P < .001）。在未接受过晚期治疗的患者（风险比，0.577; 95% CI，0.415 - 0.802）以及既往接受过最多一线内分泌治疗的晚期疾病患者（风险比，0.565; 95% CI，0.428 - 0.744）中观察到一致的治疗效果。在患有可测量疾病的患者中，ribociclib+氟维司群组的总缓解率为40.9%，安慰剂+氟维司群组为28.7%。任一组中10%的患者报告了3级不良事件（ribociclib+氟维司群vs安慰剂+氟维司群）为中性粒细胞减少症（46.6% v 0%）和白细胞减少症（13.5%对0%）; 5%患者报告的唯一4级事件是中性粒细胞减少症结论Ribociclib联合氟维司群可能是激素受体阳性/人表皮生长因子受体2-晚期乳腺癌阴性。
PurposeThis phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naive or had received up to one line of prior endocrine therapy in the advanced setting.Patients and MethodsPatients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety.ResultsA total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naive in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in 5% of patients was neutropenia (6.8% v 0%).ConclusionRibociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.