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對于大多數(shù)激素受體陽性且HER2陰性早期乳腺癌,，術(shù)后經(jīng)過現(xiàn)有標(biāo)準(zhǔn)內(nèi)分泌治療不會復(fù)發(fā)或遠(yuǎn)處轉(zhuǎn)移,。不過,，多達(dá)30%的臨床和（或）病理特征高風(fēng)險患者可能遠(yuǎn)處轉(zhuǎn)移,，大多在最初幾年,，故需要優(yōu)化治療方案以防止此類患者早期復(fù)發(fā)或發(fā)生轉(zhuǎn)移。阿貝西利是一種長期口服的細(xì)胞周期蛋白依賴型激酶CDK4和CDK6抑制劑，已于2017年9月28日被美國批準(zhǔn)用于激素受體陽性且HER2陰性晚期乳腺癌。不過,，阿貝西利用于激素受體陽性且HER2陰性高風(fēng)險早期乳腺癌術(shù)后內(nèi)分泌輔助治療的有效性和安全性尚不明確,。 2020年9月20日，美國臨床腫瘤學(xué)會《臨床腫瘤學(xué)雜志》在線發(fā)表英國皇家馬斯登醫(yī)院,、曼徹斯特大學(xué),、德國慕尼黑大學(xué)、烏爾姆大學(xué)、巴西圣保羅臨床研究中心,、日本京都大學(xué)、廣島大學(xué),、西班牙馬德里大學(xué),、馬德里腫瘤研究所,、巴塞羅納腫瘤研究所、復(fù)旦大學(xué)附屬腫瘤醫(yī)院邵志敏,、哈爾濱醫(yī)科大學(xué)附屬腫瘤醫(yī)院張清媛、墨西哥蒙特雷私立醫(yī)院,、法國西盧瓦爾河谷腫瘤研究所,、美國莎拉·坎農(nóng)研究所,、田納西州腫瘤醫(yī)院,、哈佛大學(xué)達(dá)納法伯癌癥研究所、禮來,、貝勒大學(xué),、德克薩斯腫瘤醫(yī)院,、匹茲堡大學(xué)、韓國延世大學(xué),、意大利帕多瓦大學(xué),、威尼托腫瘤研究所、悉尼馬特醫(yī)院,、澳大利亞帕特里夏·里奇癌癥治療研究中心,、比利時魯汶大學(xué)、土耳其色雷斯大學(xué)的monarchE研究報告,，探討了激素受體陽性且HER2陰性高風(fēng)險早期乳腺癌術(shù)后阿貝西利＋內(nèi)分泌輔助治療的有效性和安全性。 monarchE: A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone in Patients With High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer (NCT03155997) 該國際多中心非盲隨機(jī)對照三期臨床研究于2017年7月～2019年8月從全球38個國家地區(qū)603家醫(yī)院入組激素受體陽性且HER2陰性高風(fēng)險（陽性淋巴結(jié)≥4枚或腫瘤≥5厘米且陽性淋巴結(jié)1～3枚,、組織學(xué)分級為3或中心Ki-67≥20%）早期乳腺癌完成手術(shù),、放療和（或）化療患者5637例，按1∶1隨機(jī)分為兩組,，給予內(nèi)分泌治療±阿貝西利（每天2次150毫克連續(xù)2年）,。主要終點為無浸潤病變生存，次要終點包括無復(fù)發(fā)遠(yuǎn)處生存,、總生存,、安全性。 結(jié)果,，根據(jù)預(yù)設(shè)中期療效分析,，截至2020年3月16日，意向治療人群發(fā)生無浸潤病變生存事件323例,。 內(nèi)分泌治療±阿貝西利相比：
無浸潤病變生存曲線 無遠(yuǎn)處復(fù)發(fā)生存曲線 安全數(shù)據(jù)與阿貝西利已知安全特征一致,。 因此,，該研究結(jié)果首次證實，對于激素受體陽性且HER2陰性高風(fēng)險早期乳腺癌患者,，CDK4和CDK6抑制劑可顯著改善術(shù)后內(nèi)分泌輔助治療的無浸潤病變生存,。 對此，美國霍普金斯大學(xué)悉德尼·金梅爾綜合癌癥中心安東尼奧·卡洛斯·沃爾夫發(fā)表同期評論：CDK4和CDK6抑制劑能否成為早期乳腺癌治療的新標(biāo)準(zhǔn),？ 相關(guān)鏈接 J Clin Oncol. 2020 Sep 20. Online ahead of print. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). Stephen R. D. Johnston, Nadia Harbeck, Roberto Hegg, Masakazu Toi, Miguel Martin, Zhi Min Shao, Qing Yuan Zhang, Jorge Luis Martinez Rodriguez, Mario Campone, Erika Hamilton, Joohyuk Sohn, Valentina Guarneri, Morihito Okada, Frances Boyle, Patrick Neven, Javier Cortés, Jens Huober, Andrew Wardley, Sara M. Tolaney, Irfan Cicin, Ian C. Smith, Martin Frenzel, Desirée Headley, Ran Wei, Belen San Antonio, Maarten Hulstijn, Joanne Cox, Joyce O'Shaughnessy, Priya Rastogi; monarchE Committee Members and Investigators. Royal Marsden NHS Foundation Trust, London, United Kingdom; The Christie, University of Manchester, Manchester, United Kingdom; Artios Pharma, Cambridge, United Kingdom; LMU University Hospital, Munich, Germany; University of Ulm, Ulm, Germany; Clinica Pesquisas e Centro Sao Paulo, Sao Paulo, Brazil; Kyoto University Hospital, Kyoto, Japan; Hiroshima University Hospital, Hiroshima, Japan; Hospital General Universitario Gregorio Maranon, Universidad Complutense, Ciberonc, GEICAM, Madrid, Spain; IOB Institute of Oncology, Quiron Group, Madrid, Barcelona, and Vall d'Hebron Institute of Oncology, Barcelona, Spain; Fudan University Shanghai Cancer Center, Shanghai, China; Harbin Medical University Cancer Hospital, Harbin, China; Alivia Clinica de Alta Especialidad, Nuevo Leon, Mexico; Institut de Cancérologie de l'Ouest Pays de la Loire, Saint Herblain-Angers, France; Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Dana-Farber Cancer Institute, Boston, MA; Eli Lilly, Indianapolis, IN; Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX; University of Pittsburgh, NSABP Foundation, Pittsburgh, PA; Yonsei Cancer Center, Seoul, Korea; University of Padova, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy; Mater Hospital Sydney, Patricia Ritchie Centre for Cancer Care and Research, North Sydney, New South Wales, Australia; Universitaire Ziekenhuizen Leuven-Campus Gasthuisberg, Leuven, Belgium; Trakya University Faculty of Medicine, Edirne, Turkey. KEY OBJECTIVE: Does adding a CDK4/6 inhibitor to endocrine therapy (ET) in the adjuvant setting provide additional benefit for patients with HR+, HER2- early breast cancer (EBC)? monarchE is a global, randomized, phase III trial that evaluated the combination of the CDK4/6 inhibitor abemaciclib and standard ET among 5,637 randomly assigned patients with HR+, HER2-, node-positive EBC at high risk of early recurrence. KNOWLEDGE GENERATED: The results showed that abemaciclib added to ET significantly improved invasive disease-free survival (IDFS) in patients with high-risk EBC in the adjuvant setting. There was a 25% reduction in the risk of developing an IDFS event relative to ET alone and a 3.5% absolute improvement in 2-year IDFS rates (92.2% v 88.7%). Safety was consistent with the known safety profile of abemaciclib. RELEVANCE: If approved, abemaciclib added to standard adjuvant ET could become a new standard of care for patients with HR+, HER2- high-risk EBC. PURPOSE: Many patients with HR+, HER2- early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2- advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting. METHODS: This open-label, phase III study included patients with HR+, HER2-, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse-free survival, overall survival, and safety. RESULTS: At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone (P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib. CONCLUSION: Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2- node-positive EBC at high risk of early recurrence. DOI: 10.1200/JCO.20.02514 J Clin Oncol. 2020 Sep 20. Online ahead of print. CDK4/6 Inhibition in Early-Stage Breast Cancer: The New Standard? Antonio Carlos Wolff. The Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, MD. DOI: 10.1200/JCO.20.02688
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