5年前，MONALEESA-2研究中期分析结果表明，口服CDK4/6抑制剂瑞博西利＋芳香酶抑制剂来曲唑与安慰剂＋来曲唑相比，一线治疗激素受体阳性HER2阴性晚期乳腺癌绝经后患者的无进展生存显著延长。不过，当时该研究关键次要终点之一总生存尚未达到终点。
MONALEESA-2 (NCT01958021): A Randomized Double-blind, Placebo-controlled Study of LEE011 in Combination With Letrozole for the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease
2022年3月10日，国际四大医学期刊之首、美国麻省医学会《新英格兰医学杂志》在线发表美国德克萨斯大学MD安德森癌症中心、德克萨斯大学西南医学中心、西蒙斯综合癌症中心、贝勒大学医学中心、德克萨斯肿瘤医院、莎拉坎农研究所、佛罗里达肿瘤医院、哈佛大学达纳法伯癌症研究所、以色列特拉维夫大学拉宾医疗中心、新加坡国立癌症中心、荷兰癌症研究所、法国西部癌症研究所、勒内·高杜乔癌症中心、巴黎萨克雷大学、古斯塔夫·鲁西研究所、捷克马萨里克纪念癌症研究所、德国乌尔姆大学、意大利帕多瓦大学威尼托肿瘤研究所、英国爱丁堡大学癌症研究中心、美国诺华、瑞士诺华的MONALEESA-2研究最终分析结果，报告了瑞博西利＋来曲唑一线治疗激素受体阳性HER2阴性晚期乳腺癌绝经后患者的总生存。
该国际多中心双盲安慰剂随机对照三期临床研究于2014年1月24日～2015年3月24日从全球29个国家223家医院入组激素受体阳性HER2阴性晚期乳腺癌绝经后患者668例，按1∶1的比例随机分为两组：瑞博西利组（334例）口服瑞博西利＋来曲唑、安慰剂组（334例）口服瑞博西利＋安慰剂。通过分层对数秩检验对总生存进行评定，并于400例死亡发生后根据生存曲线进行汇总，采用分层检验策略对无进展生存和总生存进行分析，以确保研究结果的有效性。
结果，中位随访6.6年后，瑞博西利组与安慰剂组相比：
总死亡率：54.2%比65.6%（181例、219例）
总生存期：中位63.9个月比51.4个月（95%置信区间：52.4～71.0、47.2～59.7）
死亡风险：减少24%（风险比：0.76；95%置信区间：0.63～0.93，双侧P=0.008）
亚组分析表明，除了拉丁美洲地区，无论其他影响因素如何，瑞博西利组都优于安慰剂组。
未见新的安全问题。
因此，该研究结果表明，瑞博西利＋来曲唑与安慰剂＋来曲唑相比，一线治疗激素受体阳性HER2阴性晚期乳腺癌绝经后患者的总生存显著获益，中位总生存延长超过12个月！
相关链接
N Engl J Med. 2022 Mar 10;386(10):942-950.
Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer.Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, André F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J.University of Texas M.D. Anderson Cancer Center, Houston; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center; Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, Texas; Sarah Cannon Research Institute, Nashville; Florida Cancer Specialists, Sarah Cannon Research Institute, Fort Myers; Dana-Farber Cancer Institute, Boston; Institute of Oncology, Davidoff Center, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel; National Cancer Centre Singapore, Singapore; Netherlands Cancer Institute and Borstkanker Onderzoek Groep Study Center, Amsterdam; Institut de Cancérologie de l'Ouest-René Gauducheau, Saint-Herblain; Institut Gustave Roussy, Medical School, Université Paris-Saclay, Villejuif, France; Masaryk Memorial Cancer Institute, Brno, Czech; University of Ulm, Ulm, Germany; University of Padua; Istituto Oncologico Veneto, IRCCS, Padua, Italy; University of Edinburgh, Edinburgh; Novartis Pharmaceuticals, East Hanover, NJ; Novartis Pharma, Basel, Switzerland.BACKGROUND: In a previous analysis of this phase 3 trial, first-line ribociclib plus letrozole resulted in significantly longer progression-free survival than letrozole alone among postmenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether overall survival would also be longer with ribociclib was not known.METHODS: Here we report the results of the protocol-specified final analysis of overall survival, a key secondary end point. Patients were randomly assigned in a 1:1 ratio to receive either ribociclib or placebo in combination with letrozole. Overall survival was assessed with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods after 400 deaths had occurred. A hierarchical testing strategy was used for the analysis of progression-free survival and overall survival to ensure the validity of the findings.RESULTS: After a median follow-up of 6.6 years, 181 deaths had occurred among 334 patients (54.2%) in the ribociclib group and 219 among 334 (65.6%) in the placebo group. Ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole. Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, 47.2 to 59.7) with placebo plus letrozole (hazard ratio for death, 0.76; 95% CI, 0.63 to 0.93; two-sided P=0.008). No new safety signals were observed.CONCLUSIONS: First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer. Median overall survival was more than 12 months longer with ribociclib than with placebo.MONALEESA-2 ClinicalTrials.gov number: NCT01958021DOI: 10.1056/NEJMoa2114663
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