6月 08, 2022
  • Ribociclib是目前唯一在所有三项III期临床试验中观察到一致总生存期（OS）获益的CDK4/6抑制剂，拥有迄今为止在HR +/HER2-转移性乳腺癌最长的中位OS数值1-10
  • 在Ribociclib剂量按要求降低后，Ribociclib联合来曲唑一线治疗HR +/HER2转移性乳腺癌绝经后女性仍能维持OS获益11
  • 匹配校正的间接比较分析表明，与阿贝西利联合芳香化酶抑制剂（AI）相比，Ribociclib 联合AI用于一线治疗时患者的生活质量更佳12

诺华近日于2022年美国临床肿瘤学会（ASCO）年会上公布了Ribociclib联合内分泌疗法治疗激素受体阳性/人表皮生长因子受体阴性（HR +/HER2-）晚期或转移性乳腺癌患者新的总生存期（OS）和生活质量（QoL）分析数据。

在对III期MONALEESA-2研究数据进行的一项新的探索性分析中，Ribociclib 联合来曲唑在HR +/HER2-转移性乳腺癌绝经后患者（包括需要调整Ribociclib剂量的患者）的一线治疗中维持了OS获益（摘要#1017）。在该分析中，从600 mg起始剂量开始至少降低一次Ribociclib剂量的患者中观察到中位OS为66.0个月，而未降低剂量的患者为60.6个月（95% CI：分别为57.6 - 75.7和42.5 - 79.2）。此外，在接受Ribociclib联合来曲唑治疗的所有患者亚组中均观察到OS获益11.

诺华创新药物美国肿瘤执行副总裁Reshema Kemps-Polanco说：“Ribociclib是目前唯一一个在其所有III期临床研究项目中都表现出统计学意义总生存获益的CDK4/6抑制剂。”“总生存期是肿瘤学临床试验的最终目标，也是患者希望的：活得更长，活得更好。我们对Ribociclib的生活质量数据以及在HR +/HER2-转移性乳腺癌中的最长中位总生存期感到极为自豪。”

MAIC*(匹配校正的间接比较)研究表明,在HR +/HER2-转移性乳腺癌绝经后患者的一线治疗中，通过与阿贝西利联合芳香化酶抑制剂的间接相比，Ribociclib联合芳香化酶抑制剂可改善症状相关生活质量（摘要#1015）。MAIC研究结果支持Ribociclib联合芳香化酶抑制剂治疗在至持续恶化时间（TTSD）方面更优，包括食欲不振、腹泻、疲乏和手臂症状。

“作为一名治疗转移性乳腺癌患者的临床医生和临床研究人员，我一直努力寻找一种能给患者更长生存时间同时又能保持患者生活质量的疗法。”加州大学Helen Diller家庭综合癌症中心乳腺肿瘤学和临床试验教育主任、医学教授Hope S. Rugo博士说， “我们对Ribociclib 联合芳香化酶抑制剂的间接比较帮助我们初步了解了可能影响生活质量的症状，以及不同治疗选择之间的差异。”

* MAIC是在头对头试验不可及的情况下对患者人群差异校正后用于比较治疗有效性的方法。

关于Ribociclib

Ribociclib是目前唯一在所有三项III期临床研究中证实具有总生存期获益的CDK4/6抑制剂1-9, 并被美国国家综合癌症网络（NCCN）指南公认为是目前唯一在HR +/HER2-转移性乳腺癌一线治疗中具有总生存期获益的CDK4/6抑制剂13。此外，根据ESMO临床获益幅度量表（MCBS），Ribociclib在目前CDK4/6抑制剂的评分最高，绝经前HR +/HER2-转移性乳腺癌患者一线治疗的评分达到满分5分14。此外，Ribociclib联合来曲唑或氟维司群在绝经后HR +/HER2-转移性乳腺癌患者一线治疗的评分为4分15。

Ribociclib已在全球超过95个国家获批，包括美国食品药品监督管理局（FDA）和欧盟委员会，与芳香化酶抑制剂或氟维司群联合治疗HR +/HER2-晚期或转移性乳腺癌女性患者，作为基于内分泌的初始治疗或在内分泌治疗期间出现疾病进展后使用10,16。FDA批准Ribociclib联合氟维司群作为男性内分泌治疗的初始治疗或内分泌治疗后疾病进展后的治疗16。

诺华以卓越的科学、协作和关爱患者的热情来治疗乳腺癌。我们采取了大胆的研究方法，纳入了临床试验中常被忽视的患者人群，确定可能在疾病进展中发挥作用的新通路或突变，开发出不仅能维持，还能改善患者生活质量的疗法。在过去30年和今天，我们的使命是提供可以改善和延长转移性乳腺癌患者生命的治疗方法。

References

  1. Hortobagyi, et al. Overall Survival With Ribociclib Plus Letrozole in Advanced Breast Cancer. N Engl J Med 2022; 386:942-50. 
  2. Hortobagyi, 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. Presented at the European Society of Medical Oncology (ESMO) Congress, September 16-21, 2021. Abstract #LBA17. 
  3. Im, S. A. et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019; 381:307-316. 
  4. Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im S-A, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020;382(6):514–24. 
  5. Slamon, DJ, 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 (ESMO) Congress, September 29, 2019, Barcelona, Spain. Abstract #LBA7. 
  6. Slamon D, 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 (ASCO) Annual Meeting, June 5, 2021. Abstract #1001. 
  7. 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. Abstract #PD2-04. 
  8. Yardley, Denise, A. 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. Abstract #1054. 
  9. O’Shaughnessy J et al. Overall survival subgroup analysis by metastatic site from the Phase III MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with HR+/HER2− advanced breast cancer. Presented at the San Antonio Breast Cancer Symposium, December 7-10, 2021. Abstract #GS2-01. 
  10. Novartis Data on File. Novartis Pharmaceuticals Corp: 2021.
  11. Hart L, Bardia A, Beck JT, et al. Impact of ribociclib (RIB) dose modifications (mod) on overall survival (OS) in patients (pts) with HR+/HER2- advanced breast cancer (ABC) in MONALEESA(ML)-2. 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract #1017.
  12. Rugo HS, O’Shaughnessy J, Jhaveri K, et al. Quality of life (QOL) with ribociclib (RIB) plus aromatase inhibitor (AI) vs abemaciclib (ABE) plus AI as first-line (1L) treatment (tx) of hormone receptor–positive/human epidermal growth factor receptor–negative (HR+/HER2−) advanced breast cancer (ABC), assessed via matching-adjusted indirect comparison (MAIC). 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Abstract #1015.
  13. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Breast Cancer. Version 1.2022.
  14. European Society for Medical Oncology – Magnitude of Clinical Benefit Scale Scorecard. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-158-1. Published April 20, 2020. Updated August 21, 2020. Accessed September 9, 2020.
  15. European Society for Medical Oncology – Magnitude of Clinical Benefit Scale Scorecard. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-9-1. Published March 29, 2022. Accessed April 1, 2022.
  16. Kisqali (ribociclib) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation.
  17. Novartis Pharmaceuticals and Translational Research in Oncology (2018, December 7 – 2026, May 29). A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer (NATALEE). Identifier NCT03701334. https://clinicaltrials.gov/ct2/show/NCT03701334.