Dennis J. Slamon, University of California Los Angeles Medical Center, Santa Monica, CA; Patrick Neven, Multidisciplinary Breast Centre, Universitair Ziekenhuis, Leuven; Guy Jerusalem, Centre Hospitalier Universitaire de Liege and Liege University, Liège, Belgium; Stephen Chia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Peter A. Fasching, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen; Arnd Nusch, Practice for Hematology and Internal Oncology, Velbert, Germany; Michelino De Laurentiis, Istituto Nazionale Tumori "Fondazione G. Pascale," Naples; Giulia Val Bianchi, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy; Seock-Ah Im, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Katarina Petrakova, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Francisco J. Esteva, New York University Langone Health, New York, NY; Miguel Martín, Instituto de Investigacion Sanitaria Gregorio Marañon, Centro de Investigación Biomédica en Red de Cáncer, Grupo Español de Investigación en Cáncer de Mama, Universidad Complutense, Madrid; Luis De la Cruz-Merino, Hospital Universitario Virgen Macarena, Seville, Spain; Gabe S. Sonke, Netherlands Cancer Institute/Borstkanker Onderzoek Groep Study Center, Amsterdam, the Netherlands; J. Thaddeus Beck, Highlands Oncology Group, Fayetteville, AR; Xavier Pivot, Institut Régional du Cancer, Strasbourg, France; Gena Vidam, Karen Rodriguez Lorenc, Michelle Miller, and Tetiana Taran, Novartis Pharmaceuticals, East Hanover, NJ; and Yingbo Wang, Novartis Pharma, Basel, Switzerland.
J Clin Oncol. 2018 Aug 20;36(24):2465-2472. doi: 10.1200/JCO.2018.78.9909. Epub 2018 Jun 3.
Purpose This 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 naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients 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. Results A 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 naïve 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%). Conclusion Ribociclib 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.
本 III 期研究评估了在激素受体阳性/人表皮生长因子受体 2 阴性晚期乳腺癌患者中的应用，这些患者既往未接受过治疗或在晚期仅接受过一线内分泌治疗。
患者以 2:1 的比例随机分配至接受瑞博西林联合氟维司群或安慰剂联合氟维司群治疗。主要终点为局部评估的无进展生存期。次要终点包括总生存期、总缓解率和安全性。
共 484 例绝经后女性被随机分配至瑞博西林联合氟维司群组，242 例被分配至安慰剂联合氟维司群组。与安慰剂联合氟维司群组相比，瑞博西林联合氟维司群组的中位无进展生存期显著改善：20.5 个月（95%CI，18.5 至 23.5 个月）与 12.8 个月（95%CI，10.9 至 16.3 个月）（风险比，0.593；95%CI，0.480 至 0.732；P<0.001）。在晚期初治患者（风险比，0.577；95%CI，0.415 至 0.802）和晚期已接受过一线内分泌治疗的患者（风险比，0.565；95%CI，0.428 至 0.744）中观察到一致的治疗效果。在可测量疾病患者中，瑞博西林联合氟维司群组的总缓解率为 40.9%，安慰剂联合氟维司群组为 28.7%。任一治疗组中报告的≥10%患者发生的 3 级不良事件为中性粒细胞减少症（46.6%比 0%）和白细胞减少症（13.5%比 0%）；≥5%患者报告的唯一 4 级不良事件为中性粒细胞减少症（6.8%比 0%）。
瑞博西林联合氟维司群可能成为激素受体阳性/人表皮生长因子受体 2 阴性晚期乳腺癌的新一线或二线治疗选择。
