Efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy for HR<sup>+</sup>/HER2<sup>- </sup>advanced/metastatic breast cancer: A network meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

PU Yanjiao ¹ , LI Hui ¹ , CHEN Wei ¹ , DUAN Xueyu ¹ , CHEN Chunmei ² , WU Rui ¹ ,  WANG Xuechang ²

1. College of Pharmacy, Dali University, Dali, 671000, Yunnan, P. R. China;
2. Department of Pharmacy, The First People's Hospital of Anning, Kunming, 650302, P. R. China;

Corresponding author：

WANG Xuechang, Email: ynwangxc@163.com

Keywords：

HR⁺/HER2^- advanced/metastatic breast cancer; CDK4/6 inhibitor; endocrine therapy; effectiveness; safety; network meta-analysis

DOI：

10.7507/1007-4848.202311017

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR⁺)/human epidermal growth factor receptor 2-negative (HER2^-) advanced or metastatic breast cancer using network meta-analysis. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR⁺/HER2^- metastatic/advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 publications, involving 8 031 patients and 11 treatment regimens, were included. There were no significant differences in progression-free survival (PFS) and overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant differences (P<0.05) in grade 3-4 adverse events and serious adverse events were observed among certain types of CDK4/6i. Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR⁺/HER2^- advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual patient conditions.

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3.	王金燕, 杨瑒, 朱凌曦, 等. 基于患者报告结局的乳腺癌患者社会功能的特征分析研究. 解放军护理杂志, 2022, 39(7): 21-24.
4.	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. CA Cancer J Clin, 2023, 73(5): 480-515.
5.	Kay C, Martínez-Pérez C, Meehan J, et al. Current trends in the treatment of HR⁺/HER2⁺ breast cancer. Future Oncol, 2021, 17(13): 1665-1681.
6.	Watt AC, Goel S. Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Breast Cancer Res, 2022, 24(1): 17.
7.	Wang L, Gao S, Li D, et al. CDK4/6 inhibitors plus endocrine therapy improve overall survival in advanced HR+/HER2- breast cancer: A meta-analysis of randomized controlled trials. Breast J, 2020, 26(7): 1439-1443.
8.	Rugo HS, Rumble RB, Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline. J Clin Oncol, 2016, 34(25): 3069-3103.
9.	Petrelli F, Dottorini L, Di Menna G, et al. The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis. Breast, 2023, 71: 138-142.
10.	Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: A new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev, 2019, 10(10): ED000142.
11.	van Valkenhoef G, Dias S, Ades AE, et al. Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis. Res Synth Methods, 2016, 7(1): 80-93.
12.	Shim S, Yoon BH, Shin IS, et al. Network meta-analysis: Application and practice using Stata. Epidemiol Health, 2017, 39: e2017047.
13.	Zhang P, Zhang Q, Tong Z, et al. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol, 2023, 24(6): 646-657.
14.	Xu B, Zhang Q, Zhang P, et al. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: A randomized, phase 3 trial. Nat Med, 2021, 27(11): 1904-1909.
15.	Finn RS, Crown JP, Lang I, et al. 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, 2015, 16(1): 25-35.
16.	Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med, 2016, 375(20): 1925-1936.
17.	Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): Final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol, 2016, 17(4): 425-439.
18.	Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med, 2018, 379(20): 1926-1936.
19.	Xu B, Hu X, Li W, et al. Palbociclib plus letrozole versus placebo plus letrozole in Asian postmenopausal women with oestrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Primary results from PALOMA-4. Eur J Cancer, 2022, 175: 236-245.
20.	Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phaseⅢ trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol, 2018, 29(7): 1541-1547.
21.	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.
22.	Slamon DJ, Neven P, Chia S, et al. PhaseⅢ randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol, 2018, 36(24): 2465-2472.
23.	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. Ann Oncol, 2021, 32(8): 1015-1024.
24.	Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): A randomised phase 3 trial. Lancet Oncol, 2018, 19(7): 904-915.
25.	Lu YS, Im SA, Colleoni M, et al. Updated overall survival of ribociclib plus endocrine therapy versus endocrine therapy alone in pre- and perimenopausal patients with HR⁺/HER2^- advanced breast cancer in MONALEESA-7: A phase Ⅲ randomized clinical trial. Clin Cancer Res, 2022, 28(5): 851-859.
26.	Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR⁺/HER2^- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol, 2017, 35(25): 2875-2884.
27.	Sledge GW, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: A randomized clinical trial. JAMA Oncol, 2020, 6(1): 116-124.
28.	Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: A randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer, 2019, 5: 5.
29.	Zhang QY, Sun T, Yin YM, et al. MONARCH plus: Abemaciclib plus endocrine therapy in women with HR⁺/HER2^- advanced breast cancer: The multinational randomized phase Ⅲ study. Ther Adv Med Oncol, 2020, 12: 1758835920963925.
30.	Park YH, Kim TY, Kim GM, et al. Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol, 2019, 20(12): 1750-1759.
31.	Martin M, Zielinski C, Ruiz-Borrego M, et al. Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: A phaseⅢ randomised controlled trial-PEARL. Ann Oncol, 2021, 32(4): 488-499.
32.	Martín M, Zielinski C, Ruiz-Borrego M, et al. Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study. Eur J Cancer, 2022, 168: 12-24.
33.	Albanell J, Martínez MT, Ramos M, et al. Randomized phase Ⅱ study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Eur J Cancer, 2022, 161: 26-37.
34.	Robertson JFR, Bondarenko IM, Trishkina E, et al. 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.
35.	Robertson JF, Llombart-Cussac A, Rolski J, et al. Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: Results from the FIRST study. J Clin Oncol, 2009, 27(27): 4530-4535.
36.	Ellis MJ, Llombart-Cussac A, Feltl D, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: Overall survival analysis from the phase Ⅱ FIRST study. J Clin Oncol, 2015, 33(32): 3781-3787.
37.	Llombart-Cussac A, Pérez-García JM, Bellet M, et al. Fulvestrant-palbociclib vs letrozole-palbociclib as initial therapy for endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer: A randomized clinical trial. JAMA Oncol, 2021, 7(12): 1791-1799.
38.	莫淼, 黄亮, 管晓翔. 瑞博西林联合氟维司群用于激素受体阳性、人表皮生长因子受体2阴性晚期乳腺癌的Ⅲ期研究—MONALEESA3研究解读. 中国癌症杂志, 2019, 29(6): 468-475.
39.	张军, 赵崇如, 刘万立, 等. 细胞周期蛋白依赖性激酶4/6抑制剂在乳腺癌治疗中的新策略. 中华乳腺病杂志(电子版), 2022, 16(2): 110-115.
40.	Huang T, He Y, Yu C, et al. The effect and safety of CDK4/6 inhibitors combined endocrine therapy on HR⁺, HER2^-breast cancer: A meta-analysis of randomized controlled trials. Endokrynol Pol, 2023, 74(1): 89-105.
41.	Zheng J, Wu J, Wang C, et al. Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis. PLoS One, 2020, 15(6): e0233571.
42.	Hu W, Sung T, Jessen BA, et al. Mechanistic investigation of bone marrow suppression associated with palbociclib and its differentiation from cytotoxic chemotherapies. Clin Cancer Res, 2016, 22(8): 2000-2008.
43.	Zhang P, Xu B, Gui L, et al. A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer. Biomark Res, 2021, 9(1): 24.
44.	Hafner M, Mills CE, Subramanian K, et al. Multiomics profiling establishes the polypharmacology of FDA-approved CDK4/6 inhibitors and the potential for differential clinical activity. Cell Chem Biol, 2019, 26(8): 1067-1080.
45.	Braal CL, Jongbloed EM, Wilting SM, et al. Inhibiting CDK4/6 in breast cancer with palbociclib, ribociclib, and abemaciclib: Similarities and differences. Drugs, 2021, 81(3): 317-331.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3. 王金燕, 杨瑒, 朱凌曦, 等. 基于患者报告结局的乳腺癌患者社会功能的特征分析研究. 解放军护理杂志, 2022, 39(7): 21-24.
4. 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. CA Cancer J Clin, 2023, 73(5): 480-515.
5. Kay C, Martínez-Pérez C, Meehan J, et al. Current trends in the treatment of HR⁺/HER2⁺ breast cancer. Future Oncol, 2021, 17(13): 1665-1681.
6. Watt AC, Goel S. Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Breast Cancer Res, 2022, 24(1): 17.
7. Wang L, Gao S, Li D, et al. CDK4/6 inhibitors plus endocrine therapy improve overall survival in advanced HR+/HER2- breast cancer: A meta-analysis of randomized controlled trials. Breast J, 2020, 26(7): 1439-1443.
8. Rugo HS, Rumble RB, Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline. J Clin Oncol, 2016, 34(25): 3069-3103.
9. Petrelli F, Dottorini L, Di Menna G, et al. The role of CDK4/6 inhibitors in older and younger patients with breast cancer: A systematic review and meta-analysis. Breast, 2023, 71: 138-142.
10. Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: A new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev, 2019, 10(10): ED000142.
11. van Valkenhoef G, Dias S, Ades AE, et al. Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis. Res Synth Methods, 2016, 7(1): 80-93.
12. Shim S, Yoon BH, Shin IS, et al. Network meta-analysis: Application and practice using Stata. Epidemiol Health, 2017, 39: e2017047.
13. Zhang P, Zhang Q, Tong Z, et al. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol, 2023, 24(6): 646-657.
14. Xu B, Zhang Q, Zhang P, et al. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: A randomized, phase 3 trial. Nat Med, 2021, 27(11): 1904-1909.
15. Finn RS, Crown JP, Lang I, et al. 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, 2015, 16(1): 25-35.
16. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med, 2016, 375(20): 1925-1936.
17. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): Final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol, 2016, 17(4): 425-439.
18. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med, 2018, 379(20): 1926-1936.
19. Xu B, Hu X, Li W, et al. Palbociclib plus letrozole versus placebo plus letrozole in Asian postmenopausal women with oestrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Primary results from PALOMA-4. Eur J Cancer, 2022, 175: 236-245.
20. Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phaseⅢ trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol, 2018, 29(7): 1541-1547.
21. 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.
22. Slamon DJ, Neven P, Chia S, et al. PhaseⅢ randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol, 2018, 36(24): 2465-2472.
23. 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. Ann Oncol, 2021, 32(8): 1015-1024.
24. Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): A randomised phase 3 trial. Lancet Oncol, 2018, 19(7): 904-915.
25. Lu YS, Im SA, Colleoni M, et al. Updated overall survival of ribociclib plus endocrine therapy versus endocrine therapy alone in pre- and perimenopausal patients with HR⁺/HER2^- advanced breast cancer in MONALEESA-7: A phase Ⅲ randomized clinical trial. Clin Cancer Res, 2022, 28(5): 851-859.
26. Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR⁺/HER2^- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol, 2017, 35(25): 2875-2884.
27. Sledge GW, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: A randomized clinical trial. JAMA Oncol, 2020, 6(1): 116-124.
28. Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: A randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer, 2019, 5: 5.
29. Zhang QY, Sun T, Yin YM, et al. MONARCH plus: Abemaciclib plus endocrine therapy in women with HR⁺/HER2^- advanced breast cancer: The multinational randomized phase Ⅲ study. Ther Adv Med Oncol, 2020, 12: 1758835920963925.
30. Park YH, Kim TY, Kim GM, et al. Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol, 2019, 20(12): 1750-1759.
31. Martin M, Zielinski C, Ruiz-Borrego M, et al. Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: A phaseⅢ randomised controlled trial-PEARL. Ann Oncol, 2021, 32(4): 488-499.
32. Martín M, Zielinski C, Ruiz-Borrego M, et al. Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study. Eur J Cancer, 2022, 168: 12-24.
33. Albanell J, Martínez MT, Ramos M, et al. Randomized phase Ⅱ study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Eur J Cancer, 2022, 161: 26-37.
34. Robertson JFR, Bondarenko IM, Trishkina E, et al. 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.
35. Robertson JF, Llombart-Cussac A, Rolski J, et al. Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: Results from the FIRST study. J Clin Oncol, 2009, 27(27): 4530-4535.
36. Ellis MJ, Llombart-Cussac A, Feltl D, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: Overall survival analysis from the phase Ⅱ FIRST study. J Clin Oncol, 2015, 33(32): 3781-3787.
37. Llombart-Cussac A, Pérez-García JM, Bellet M, et al. Fulvestrant-palbociclib vs letrozole-palbociclib as initial therapy for endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer: A randomized clinical trial. JAMA Oncol, 2021, 7(12): 1791-1799.
38. 莫淼, 黄亮, 管晓翔. 瑞博西林联合氟维司群用于激素受体阳性、人表皮生长因子受体2阴性晚期乳腺癌的Ⅲ期研究—MONALEESA3研究解读. 中国癌症杂志, 2019, 29(6): 468-475.
39. 张军, 赵崇如, 刘万立, 等. 细胞周期蛋白依赖性激酶4/6抑制剂在乳腺癌治疗中的新策略. 中华乳腺病杂志(电子版), 2022, 16(2): 110-115.
40. Huang T, He Y, Yu C, et al. The effect and safety of CDK4/6 inhibitors combined endocrine therapy on HR⁺, HER2^-breast cancer: A meta-analysis of randomized controlled trials. Endokrynol Pol, 2023, 74(1): 89-105.
41. Zheng J, Wu J, Wang C, et al. Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis. PLoS One, 2020, 15(6): e0233571.
42. Hu W, Sung T, Jessen BA, et al. Mechanistic investigation of bone marrow suppression associated with palbociclib and its differentiation from cytotoxic chemotherapies. Clin Cancer Res, 2016, 22(8): 2000-2008.
43. Zhang P, Xu B, Gui L, et al. A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer. Biomark Res, 2021, 9(1): 24.
44. Hafner M, Mills CE, Subramanian K, et al. Multiomics profiling establishes the polypharmacology of FDA-approved CDK4/6 inhibitors and the potential for differential clinical activity. Cell Chem Biol, 2019, 26(8): 1067-1080.
45. Braal CL, Jongbloed EM, Wilting SM, et al. Inhibiting CDK4/6 in breast cancer with palbociclib, ribociclib, and abemaciclib: Similarities and differences. Drugs, 2021, 81(3): 317-331.

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Latest ArticlesEfficacy and safety of CDK4/6 inhibitors combined with endocrine therapy for HR⁺/HER2^-advanced/metastatic breast cancer: A network meta-analysis

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Latest ArticlesEfficacy and safety of CDK4/6 inhibitors combined with endocrine therapy for HR+/HER2- advanced/metastatic breast cancer: A network meta-analysis

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Latest ArticlesEfficacy and safety of CDK4/6 inhibitors combined with endocrine therapy for HR⁺/HER2^-advanced/metastatic breast cancer: A network meta-analysis