Objective  To evaluate the cost-effectiveness of the combination therapy of ribociclib plus fulvestrant compared to fulvestrant monotherapy as a second-line treatment for postmenopausal patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced metastatic breast cancer from the perspective of the Chinese healthcare system.

Methods  A partitioned survival model was constructed based on MONALEESA-3 study data, with the model cycle of 4 weeks and the time range of 15 years. Total cost, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were compared between ribociclib combined with fulvestrant and fulvestrant monotherapy as a second-line treatment for postmenopausal patients with HR+/HER2- advanced metastatic breast cancer. The robustness of the models was validated through one-way sensitivity analysis and probabilistic sensitivity analysis.

Results  Compared with the fulvestrant monotherapy regimen, the ICER for the ribociclib combined with fulvestrant regimen was 187,958.06 yuan/QALY, which was below the willingness-to-pay (WTP) threshold of three times China’s per capita gross domestic product (GDP) in 2024 (287,247 yuan/QALY). The one-way sensitivity analysis revealed that the ICER was primarily influenced by the proportion of patients receiving subsequent treatments with the combination therapy or fulvestrant monotherapy, and the utility value of progression-free survival. The probabilistic sensitivity analysis showed that at a WTP threshold of three times China’s per capita GDP in China in 2024 (287,247 yuan/QALY), the probability of the ribociclib combination therapy being cost-effective was 100%.

Conclusion  In the context of the Chinese healthcare system, the combination therapy of ribociclib and fulvestrant is more cost-effective than fulvestrant monotherapy for the second-line treatment of postmenopausal patients with HR+/HER2- advanced metastatic breast cancer.

1.Huppert LA, Gumusay O, Idossa D, et al. Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer[J]. CA Cancer J Clin, 2023, 73(5): 480-515. DOI: 10.3322/caac.21777.

2.Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer[J]. Cancer Cell, 2020, 37(4): 496-513. DOI: 10.1016/j.ccell.2020.03.009.

3.Álvarez-Fernández M, Malumbres M. Mechanisms of sensitivity and resistance to CDK4/6 inhibition[J]. Cancer Cell, 2020, 37(4): 514-529. DOI: 10.1016/j.ccell.2020.03.010.

4.Spring LM, Wander SA, Andre F, et al. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future[J]. Lancet, 2020, 395(10226): 817-827. DOI: 10.1016/s0140-6736(20)30165-3.

5.饶彬, 吴耀忠. CDK4/6抑制剂在晚期乳腺癌内分泌治疗的临床研究进展[J]. 中国现代医生, 2021, 59(26): 188-192. [Rao B, Wu YZ. Progress in clinical research of CDK4/6 inhibitors in endocrine therapy of advanced breast cancer[J]. China Modern Doctor, 2021, 59(26): 188-192.] https://d.wanfangdata.com.cn/periodical/zwkjzlml-yyws202126045.

6.Slamon DJ, Neven P, Chia S, et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase Ⅲ randomized MONALEESA-3 trial: updated overall survival[J]. Ann Oncol, 2021, 32(8): 1015-1024. DOI: 10.1016/j.annonc.2021.05.353.

7.Neven P, Fasching PA, Chia S, et al. Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2- advanced breast cancer receiving first-line ribociclib plus fulvestrant[J]. Breast Cancer Res, 2023, 25(1): 103. DOI: 10.1186/s13058-023-01701-9.

8.Slamon DJ, Neven P, Chia S, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer[J]. N Engl J Med, 2020, 382(6): 514-524. DOI: 10.1056/NEJMoa1911149.

9.Jiang W, He Z, Zhang T, et al. Cost-effectiveness analysis of ribociclib plus fulvestrant for hormone receptor-positive/human EGF receptor 2-negative breast cancer[J]. Immunotherapy, 2021, 13(8): 661-668. DOI: 10.2217/imt-2020-0237.

10.Wang Y, Rui M, Guan X, et al. Cost-effectiveness analysis of abemaciclib plus fulvestrant in the second-line treatment of women with HR+/HER2- advanced or metastatic breast cancer: a US payer perspective[J]. Front Med (Lausanne), 2021, 8: 658747. DOI: 10.3389/fmed.2021.658747.

11.Jeong E, Wang C, Wilson L, et al. Cost-effectiveness of adding ribociclib to endocrine therapy for patients with HR-positive, HER2-negative advanced breast cancer among premenopausal or perimenopausal women[J]. Front Oncol, 2021, 11: 658054. DOI: 10.3389/fonc.2021.658054.

12.Guyot P, Ades AE, Ouwens MJ, et al. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves[J]. BMC Med Res Methodol, 2012, 12: 9. DOI: 10.1186/1471-2288-12-9.

13.Latimer NR. Survival analysis for economic evaluations alongside clinical trials--extrapolation with patient-level data: inconsistencies, limitations, and a practical guide[J]. Med Decis Making, 2013, 33(6): 743-754. DOI: 10.1177/0272989x12472398.

14.石丰豪, 商叶, 芮明军, 等. R语言survHE程序包在卫生经济学评价中的应用[J]. 中国卫生经济, 2020, 39(9): 9-14. [Shi FH, Shang Y, Rui MJ, et al. Health economics researchapplication of SurvHE package of R for health economic evaluation[J]. Chinese Health Economics, 2020, 39(9): 9-14.] DOI: 10.7664/CHE20200902.

15.刘国恩, 主编. 中国药物经济学评价指南2020[M]. 北京: 中国市场出版社, 2020: 36-46.

16.国家统计局. 中华人民共和国2024年国民经济和社会发展统计公报[EB/OL]. (2025-02-28) [2025-04-01]. https://www.stats.gov.cn/sj/zxfb/202502/t20250228_1958817.html.

17.Ding H, Fang L, Xin W, et al. Cost-effectiveness analysis of fulvestrant versus anastrozole as first-line treatment for hormone receptor-positive advanced breast cancer[J]. Eur J Cancer Care (Engl), 2017, 26(6): 1. DOI: 10.1111/ecc.12733.

18.Wang H, Wang Y, Gong R, et al. Cost-effectiveness of pertuzumab and trastuzumab as a first-line treatment of HER2-positive metastatic breast cancer in China[J]. Ann Palliat Med, 2021, 10(11): 11382-11393. DOI: 10.21037/apm-21-2412.

19.Wu B, Zhang Q, Sun J. Cost-effectiveness of nivolumab plus ipilimumab as first-line therapy in advanced renal-cell carcinoma[J]. J Immunother Cancer, 2018, 6(1): 124. DOI: 10.1186/s40425-018-0440-9.

20.Zhou T, Cao Y, Wang X, et al. Economic evaluation of sintilimab plus bevacizumab versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma[J]. Adv Ther, 2022, 39(5): 2165-2177. DOI: 10.1007/s12325-022-02079-4.

21.中国居民营养与慢性病状况报告（2020年）[J]. 营养学报, 2020, 42(6): 521. https://kns.cnki.net/kcms2/article/abstract?v=tQ02qvqxHS-L2jfX6HP8pCn3JYb_WEa-n-zkNEO9XZ2C9pj0B6r3QWehLZd8f5FR73GAc0QGhnxPhn7vLKVkRB1S9jx9fkN90BKPvPwQxGP-lJB6b1elpXyWk-ZXO4cNLVRMzvMBVg-Pw-T8NgNmSdbcjyAR9LJr0gW3h7kXet3LFq_kezIZ_Q==&uniplatform=NZKPT&language=CHS.

22.Mistry R, May JR, Suri G, et al. Cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole and letrozole monotherapy in the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer: a U.S. payer perspective[J]. J Manag Care Spec Pharm, 2018, 24(6): 514-523. DOI: 10.18553/jmcp.2018.24.6.514.

23.Lloyd A, Nafees B, Narewska J, et al. Health state utilities for metastatic breast cancer[J]. Br J Cancer, 2006, 95(6): 683-690. DOI: 10.1038/sj.bjc.6603326.

24.Huang X, Lin S, Rao X, et al. First-line treatment with ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive advanced breast cancer: a cost-effectiveness analysis[J]. Clin Breast Cancer, 2021, 21(4): e479-e488. DOI: 10.1016/j.clbc.2021.01.019.

25.Launois R, Reboul-Marty J, Henry B, et al. A cost-utility analysis of second-line chemotherapy in metastatic breast cancer. Docetaxel versus paclitaxel versus vinorelbine[J]. Pharmacoeconomics, 1996, 10(5): 504-521. DOI: 10.2165/00019053-199610050-00008.

26.Slamon DJ, Neven P, Chia S, et al. Phase Ⅲ randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3[J]. J Clin Oncol, 2018, 36(24): 2465-2472. DOI: 10.1200/jco.2018.78.9909.

27.Zhou T, Cao Y, Wang X, et al. Economic evaluation of sintilimab plus bevacizumab versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma[J]. Adv Ther, 2022, 39(5): 2165-2177. DOI: 10.1007/s12325-022-02079-4.

28.邵荣杰, 唐文熙, 马爱霞. 分区生存模型在药物经济学评价中的应用[J]. 中国卫生经济, 2019, 38(9): 60-63. [Shao RJ, Tang WX, Ma AX. The partitioned survival model applied in pharmacoeconomic evaluation[J]. Chinese Health Economics, 2019, 38(9): 60-63.] DOI: 10.7664/CHE20190916.

29.刘新义, 谭重庆, 曾小慧, 等. 分区生存模型在药物经济学评价中的应用简介及实例解析[J].中国现代应用药学, 2019, 36(24): 3090-3093. [Liu XY, Tan CQ, Zeng XH, et al. Introduction of partitioned survival model in pharmacoeconomics evaluation and case analysis[J]. Chinese Journal of Modern Applied Pharmacy, 2019, 36(24): 3090-3093.] DOI: 10.13748/j.cnki.issn1007-7693.2019.24.018.

30.Gupta N, Gupta D, Dixit J, et al. Cost Effectiveness of ribociclib and palbociclib in the second-line treatment of hormone receptor-positive, HER2-negative metastatic breast cancer in post-menopausal indian women[J]. Appl Health Econ Health Policy, 2022, 20(4): 609-621. DOI: 10.1007/s40258-022-00731-2.

31.Berrios K, Burum A, Jeong E, et al. Is adding ribociclib to fulvestrant cost-effective in treating postmenopausal women with HR+/HER2- advanced or metastatic breast cancer? A US payer perspective cost utility analysis[J]. J Manag Care Spec Pharm, 2022, 28(11): 1282-1291. DOI: 10.18553/jmcp.2022.28.11.1282.

32.Stellato D, Thabane ME, Park J, et al. Cost effectiveness of ribociclib in combination with fulvestrant for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer who have received no or only one prior line of endocrine therapy: a canadian healthcare perspective[J]. Pharmacoeconomics, 2021, 39(9): 1045-1058. DOI: 10.1007/s40273-021-01027-4.

33.贾才凤, 冯章英, 张森, 等. 阿贝西利联合氟维司群二线治疗激素受体阳性的晚期乳腺癌的药物经济学评价[J].中国现代应用药学, 2023, 40(12): 1609-1614. [Jia CF, Feng ZY, Zhang S, et al. Pharmacoeconomic evaluation of abemaciclib in combination with fulvestrant for second-line treatment of hormone receptor-positive advanced breast cancer[J]. Chinese Journal of Modern Applied Pharmacy, 2023, 40(12): 1609-1614.] DOI: 10.13748/j.cnki.issn1007-7693.20222787.

34.Shen L, Zhou J, Chen Y, et al. Treatment patterns, effectiveness, and patient-reported outcomes of palbociclib therapy in Chinese patients with advanced breast cancer: a multicenter ambispective real-world study[J]. Cancer Med, 2022, 11(22): 4157-4168. DOI: 10.1002/cam4.4767.