凯丽隆®获美国FDA批准用于治疗HR+/HER2-早期乳腺癌

凯丽隆^®（瑞波西利）早期适应症人群广泛（HR+/HER2-II期和III期乳腺癌的高复发风险人群），使得符合CDK4/6抑制剂辅助治疗的人群几乎翻倍^1,2_。

凯丽隆^®（瑞波西利）相较单独使用内分泌（ET）治疗显著降低复发风险25%；在关键性3期NATALEE临床研究中，包含无淋巴结转移(N0)在内的所有亚组均观察到一致的获益和良好的安全性^3-6。

最近ESMO会议上发布NATALEE重磅研究数据：在三年治疗期结束后，所有亚组的无侵袭性疾病生存（iDFS）获益更为明显⁷。

接受辅助ET治疗的II期或III期HR+/HER2-早期乳腺癌患者，无论是否有淋巴结转移，仍面临显著的复发风险，极大可能转变为不可治愈的转移性疾病^8,9。

作为一项已被证实的HR+/HER2-转移性乳腺癌治疗方案^1,10-20，目前在包括欧盟在内的全球范围正在对凯丽隆^®早期乳腺癌适应症进行注册审查。

诺华宣布，美国食品药品监督管理局（FDA）已批准凯丽隆^®（瑞波西利）与芳香化酶抑制剂（AI）联合用于HR+/HER2-II期和III期高复发风险早期乳腺癌患者的辅助治疗，包括N0的患者¹。这一批准基于关键性3期NATALEE研究的结果，该研究显示在接受辅助瑞波西利加ET的广泛HR+/HER2-II期和III期早期乳腺癌患者中，相较单独使用ET治疗，疾病复发风险显著降低25.1%（HR=0.749；95%CI:0.628, 0.892；P=0.0006），包括高风险的N0患者^3-6。在所有患者亚组中均一致的观察到iDFS获益^3-6。

UCLA Jonsson综合癌症中心临床/转化研究主任，转化肿瘤研究委员会（TRIO）主席兼 NATALEE试验首席研究员Dennis J. Slamon 医学博士

FDA批准凯丽隆^®（瑞波西利）用于治疗这部分早期乳腺癌患者，甚至包括N0的患者，这是改善治疗方法的关键时刻。今天的获批为我们向更广泛人群制定CDK4/6抑制剂联合ET治疗方案提供了强有力证据，可以帮助他们降低复发风险。

在早期乳腺癌中，瑞波西利用法用量为每日一次、每次口服400mg，用药三周后停药一周，患者持续服药三年。NATALEE研究显示，400mg瑞波西利耐受性良好，停药的主要原因是无症状的实验室检查结果异常³。瑞波西利+ET治疗组中，特别关注的不良事件（AEs）包括：中性粒细胞减少症（62.5% vs 44.3%）、与肝脏相关的不良事件（26.4% vs 8.6%）、QT间期延长（5.3% vs 1.0%）和间质性肺病/肺炎（1.5% vs 0.0%）⁴。

2024年欧洲肿瘤内科学会（ESMO）大会展示了 NATALEE研究的最新数据，结果显示，三年治疗期结束后的获益进一步加强，在II期和III期 HR+/HER2-早期乳腺癌患者中相较单独使用ET，复发风险降低28.5%（HR=0.715；95%CI 0.609–0.840；P<0.0001）⁷。诺华将继续评估NATALEE 患者的长期结果，包括总生存期。

提高早期乳腺癌患者治愈机会

早期乳腺癌以治愈为目的^21,22，但尽管如此，II期和III期HR+/HER2- 早期乳腺癌患者仍然有复发风险, 极大可能转变为不可治愈的转移性疾病^8,9。大多数肿瘤在最初几年内复发，甚至在没有淋巴结累及的病例中，复发仍然是一个终生的问题^8,23。即使有ET治疗, 仍有10%的N0伴高危因素患者在前三年内可能面临复发²⁴。

关于NATALEE

NATALEE是一项全球多中心、随机、开放标签的III期试验，旨在评估凯丽隆^®（ribociclib）与内分泌治疗（ET）作为辅助治疗与单独ET在II期和III期 HR+/HER2-早期乳腺癌患者中的疗效和安全性。该试验与转化肿瘤研究委员会（TRIO）合作进行²⁵。两组联合的辅助内分泌治疗均为非甾体类芳香化酶抑制剂（NSAI；阿那曲唑或来曲唑）和促性腺激素释放激素激动剂（如适用）²⁵。NATALEE的主要终点是根据标准疗效终点（STEEP）标准定义的无侵袭性疾病生存期（iDFS）²⁵。该试验中来自20个国家共5,101名 HR+/HER2-早期乳腺癌成年患者被随机分组²⁵。

关于诺华

诺华是一家全球领先的创新药物公司。我们的使命是创想医药未来，改善人们生活质量，延长人类寿命。2023年，全球有约2.84亿患者受益于诺华的产品。秉持“承诺中华”的理念，诺华从研发、生产到业务发展，全面布局中国市场。我们致力于为中国患者提供高临床价值的创新药。自1987年以来，诺华已有超过100款创新药物及新适应症在华获批。通过深化与中国医疗生态系统各方的多方位合作，诺华不断助力提升疾病诊疗标准，积极履行企业责任，推动健康中国战略的实施，从而为中国发展做出切实而积极的贡献。

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1.本文提及的相关适应症在中国尚未获批。

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3.本资料中涉及的信息仅供参考，请遵从医生或其他医疗卫生专业人士的意见或指导。

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— 参考文献 — （滑动查看更多）

1. Kisqali (ribociclib) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; September 2024.

2. Tarantino P, Rugo HS, Curigliano G, et al. Characteristics of real-world NATALEE and monarchE eligible populations: A US electronic health records database analysis. Poster presented at the European Society for Medical Oncology Congress; September 13-17, 2024; Barcelona, Spain.

3. Slamon D, Stroyakovskiy D, Yardley D, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2− early breast cancer: primary results from the Phase III NATALEE trial. Presented at the American Society of Clinical Oncology Annual Meeting; June 2, 2023; Chicago, USA.

4. Hortobagyi G, Stroyakovskiy D, Yardley DA, et al. Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2- early breast cancer: final invasive disease-free survival (iDFS) analysis from the NATALEE trial. Presented at San Antonio Breast Cancer Symposium (SABCS); December 8, 2023; San Antonio, USA.

5. Slamon D et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med. 2024;390:1080-1091. doi: 10.1056/NEJMoa2305488

6. Yardley D, Untch M, et al. Baseline (BL) characteristics and efficacy endpoints for patients (pts) with node-negative (N0) HR+/HER2− early breast cancer (EBC) in NATALEE. Presented at the American Society of Clinical Oncology Annual Meeting; May 31, 2024; Chicago, USA.

7. Fasching PA. Adjuvant Ribociclib (RIB) Plus Nonsteroidal Aromatase Inhibitor (NSAI) in Patients (Pts) With HR+/HER2− Early Breast Cancer (EBC): 4-Year Outcomes From the NATALEE Trial. LBA13. Proffered Paper presented at the European Society for Medical Oncology Congress; September 16, 2024; Barcelona, Spain.

8. Pan H et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017;377 (suppl 19):1836 846. doi: 10.1056/NEJMoa1701830

9. Wangchinda P, Ithimakin S. Factors that predict recurrence later than 5 years after initial treatment in operable breast cancer. World J Surg Oncol. 2016;14(1):223. doi: 10.1186/s12957-016-0988-0

10. Yardley DA, Yap YS, et al. Pooled exploratory analysis of survival in patients (pts) with HR+/HER2- advanced breast cancer (ABC) and visceral metastases (mets) treated with ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) trials. Poster presented at the European Society of Medical Oncology Congress; September 9-13, 2022; Paris, France.

11. Neven P, Fasching PA, et al. Updated overall survival (OS) results from the first-line (1L) population in the Phase III MONALEESA-3 trial of postmenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL). Mini oral presented at the European Society for Medical Oncology Breast Cancer Congress; May 4, 2022; Paris, France.

12. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663

13. Hortobagyi GN, et al. Overall survival (OS) results from the phase III MONALEESA (ML)-2 trial of postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Proffered paper presented at the European Society of Medical Oncology Congress; September 16-21, 2021; Lugano, Switzerland.

14. Im S-A, Lu Y-S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307-316. doi:10.1056/nejmoa1903765

15. Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149

16. Slamon DJ, Neven P, Chia S, et al. Overall survival (OS) results of the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor 2–negative (HER2−) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). Presented at the European Society of Medical Oncology Congress; September 29, 2019; Barcelona, Spain.

17. Slamon DJ, Neven P, Chia S, et al. Updated overall survival (OS) results from the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB. Presented at the American Society of Clinical Oncology Annual Meeting; June 5, 2021; Chicago, USA.

18. Tripathy D, Im S-A, Colleoni M, et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at the San Antonio Breast Cancer Symposium; December 9, 2020; San Antonio, USA.

19. Yardley D, Nusch A, Yap YS, et al. Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting; June 2020; Chicago, USA.

20. O’Shaughnessy J, Stemmer SM, Burris HA, et al. Overall survival subgroup analysis by metastatic site from the Phase III MONALEESA-2 study of first-line ribociclib + letroz21ole in postmenopausal patients with HR+/HER2− advanced breast cancer. Presented at the San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, USA.

21. Iqbal J, Ginsburg O, Rochon PA, Sun P, Narod SA. Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States [published correction appears in JAMA. 2015 Jun 9;313(22):2287]. JAMA. 2015;313(2):165-173. doi:10.1001/jama.2014.17322

22. American Cancer Society. Cancer Facts and Figures. Published 2024. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf. Accessed September 2024.

23. Gomis R, Gawrzak S. Tumor cell dormancy. Mol Oncol. 2017;11(1):62-78.

24. Curigliano G, Ciruelos E, et al. Meta analysis of ET control arms in adjuvant trials. Presented at the American Society of Clinical Oncology Annual Meeting; May 31, 2024; Chicago, USA.

25. Clinicaltrials.gov. NCT03701334. A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/ HER2- Early Breast Cancer (NATALEE). Accessed September 2024. https://clinicaltrials.gov/study/NCT03701334