Comparative Efficacy of CDK4/6 Inhibitors Plus Aromatase Inhibitors Versus Fulvestrant for the First-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer: A Network Meta-Analysis

Overview

Journal Target Oncol

Specialty Oncology

Date 2019 Apr 4

PMID 30941621

Citations 11

Authors

Qianqian Guo

Xiaojie Lin

Lingling Ye

Rui Xu

Yan Dai

Yuzhu Zhang

Qianjun Chen

Affiliations

Soon will be listed here.

Abstract

Background: Several endocrine therapies are available for postmenopausal women with hormone receptor-positive (HR +) advanced breast cancer (ABC). Given the absence of direct comparisons between fulvestrant and cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with aromatase inhibitors (AIs), which are both used as standard first-line treatments for ABC, an indirect comparison using a network meta-analysis may be advantageous for decision making.

Objective: We performed a network meta-analysis to compare the efficacies of fulvestrant and CDK4/6is plus AIs as the first-line treatment of postmenopausal breast cancer patients.

Patients And Methods: In order to compare these treatments, we searched the PubMed, Cochrane Library, and EMBASE databases for randomized controlled trials of first-line endocrine treatment for advanced or metastatic breast cancer until October 2018. We included a total of 11 eligible trials with 5448 patients. The hazard ratios (HRs) for the efficacies of the different treatments were used as inputs in the network meta-analysis.

Results: In the overall analysis, CDK4/6is plus AIs, including palbociclib plus letrozole, ribociclib plus letrozole, and abemaciclib plus nonsteroidal AI (letrozole or anastrozole), are all superior to 500 mg fulvestrant (HR = 0.50, 95% confidence interval [CI] 0.37-0.68; HR = 0.50, 95% CI 0.35-0.71; and HR = 0.49, 95% CI 0.34-0.71; respectively).

Conclusions: Within the limitations of this network meta-analysis, the comparison indicates that CDK4/6is plus AIs might represent a better option for HR+ ABC as a first-line endocrine treatment compared with fulvestrant.

Citing Articles

Autophagy and senescence facilitate the development of antiestrogen resistance in ER positive breast cancer.

McGrath M, Abolhassani A, Guy L, Elshazly A, Barrett J, Mivechi N Front Endocrinol (Lausanne). 2024; 15:1298423.

PMID: 38567308 PMC: 10986181. DOI: 10.3389/fendo.2024.1298423.

Haematopoietic cytopenia associated with cyclin-dependent kinase 4/6 inhibitors: A real-world study of data from the food and drug administration adverse event reporting system database.

Ren X, Yan C, Tian L, Cui X Int J Immunopathol Pharmacol. 2022; 36:3946320221145520.

PMID: 36565299 PMC: 9793014. DOI: 10.1177/03946320221145520.

Cost-Effectiveness Analysis of Abemaciclib plus Fulvestrant versus Placebo plus Fulvestrant in Patients with Hormone Receptor-Positive, ERBB2-Negative Breast Cancer.

Xie Q, Zheng H, Li Q Breast Care (Basel). 2022; 17(3):237-243.

PMID: 35957949 PMC: 9247558. DOI: 10.1159/000518551.

Role of CDK4/6 inhibitors in patients with hormone receptor (HR)-positive, human epidermal receptor-2 negative (HER-2) metastatic breast cancer study protocol for a systematic review, network meta-analysis and cost-effectiveness analysis.

Hu Q, Kang W, Wang Q, Luo T BMJ Open. 2022; 12(5):e056374.

PMID: 35636793 PMC: 9152932. DOI: 10.1136/bmjopen-2021-056374.

Expanding the Clinical Use of CDK4/6 Inhibitors in the Treatment of Hormone Receptor-Positive, HER2-Negative Breast Cancer from Metastatic Setting to Adjuvant Setting.

Abdel-Razeq H, Sharaf B Drug Des Devel Ther. 2022; 16:727-735.

PMID: 35321498 PMC: 8935948. DOI: 10.2147/DDDT.S356757.

References

Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko I, Khasanov R . Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2013; 106(1):djt337. PMC: 3906991. DOI: 10.1093/jnci/djt337. View

Glenny A, Altman D, Song F, Sakarovitch C, Deeks J, DAmico R . Indirect comparisons of competing interventions. Health Technol Assess. 2005; 9(26):1-134, iii-iv. DOI: 10.3310/hta9260. View

Woods B, Hawkins N, Scott D . Network meta-analysis on the log-hazard scale, combining count and hazard ratio statistics accounting for multi-arm trials: a tutorial. BMC Med Res Methodol. 2010; 10:54. PMC: 2906500. DOI: 10.1186/1471-2288-10-54. View

Sutton A, Ades A, Cooper N, Abrams K . Use of indirect and mixed treatment comparisons for technology assessment. Pharmacoeconomics. 2008; 26(9):753-67. DOI: 10.2165/00019053-200826090-00006. View

Alves C, Elias D, Lyng M, Bak M, Kirkegaard T, Lykkesfeldt A . High CDK6 Protects Cells from Fulvestrant-Mediated Apoptosis and is a Predictor of Resistance to Fulvestrant in Estrogen Receptor-Positive Metastatic Breast Cancer. Clin Cancer Res. 2016; 22(22):5514-5526. DOI: 10.1158/1078-0432.CCR-15-1984. View

Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A . Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol. 2001; 19(10):2596-606. DOI: 10.1200/JCO.2001.19.10.2596. View

Finn R, Martin M, Rugo H, Jones S, Im S, Gelmon K . Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016; 375(20):1925-1936. DOI: 10.1056/NEJMoa1607303. View

Zhang T, Feng F, Zhao W, Tian J, Yao Y, Zhou C . Effect of first-line endocrine therapy in patients with hormone-sensitive advanced breast cancer: a network meta-analysis. Onco Targets Ther. 2018; 11:2647-2656. PMC: 5951224. DOI: 10.2147/OTT.S165681. View

Turner N, Ro J, Andre F, Loi S, Verma S, Iwata H . Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015; 373(3):209-19. DOI: 10.1056/NEJMoa1505270. View

10.

Scott S, Lee S, Abraham J . Mechanisms of therapeutic CDK4/6 inhibition in breast cancer. Semin Oncol. 2018; 44(6):385-394. DOI: 10.1053/j.seminoncol.2018.01.006. View

11.

Robertson J, Lindemann J, Llombart-Cussac A, Rolski J, Feltl D, Dewar J . Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized 'FIRST' study. Breast Cancer Res Treat. 2012; 136(2):503-11. DOI: 10.1007/s10549-012-2192-4. View

12.

Robertson J, Bondarenko I, Trishkina E, Dvorkin M, Panasci L, Manikhas A . Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016; 388(10063):2997-3005. DOI: 10.1016/S0140-6736(16)32389-3. View

13.

Hortobagyi G, Stemmer S, Burris H, Yap Y, Sonke G, Paluch-Shimon S . Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375(18):1738-1748. DOI: 10.1056/NEJMoa1609709. View

14.

Goetz M, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J . MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017; 35(32):3638-3646. DOI: 10.1200/JCO.2017.75.6155. View

15.

Turner N, Finn R, Martin M, Im S, DeMichele A, Ettl J . Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases. Ann Oncol. 2018; 29(3):669-680. PMC: 5888946. DOI: 10.1093/annonc/mdx797. View

16.

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

17.

Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E . Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012; 23 Suppl 7:vii11-9. DOI: 10.1093/annonc/mds232. View

18.

Finn R, Crown J, Lang I, Boer K, Bondarenko I, Kulyk S . The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2014; 16(1):25-35. DOI: 10.1016/S1470-2045(14)71159-3. View

19.

Kwapisz D . Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib. Breast Cancer Res Treat. 2017; 166(1):41-54. DOI: 10.1007/s10549-017-4385-3. View

20.

Ramos-Esquivel A, Hernandez-Steller H, Savard M, Landaverde D . Cyclin-dependent kinase 4/6 inhibitors as first-line treatment for post-menopausal metastatic hormone receptor-positive breast cancer patients: a systematic review and meta-analysis of phase III randomized clinical trials. Breast Cancer. 2018; 25(4):479-488. DOI: 10.1007/s12282-018-0848-6. View