Fulvestrant in the treatment of luminal HER-2-negative metastatic breast cancer

Hormonal therapy is an effective treatment for luminal HER2-negative metastatic breast cancer (mBC). Aromatase inhibitors and fulvestrant are the mainstays of hormone therapy. Fulvestrant is both a competitive antagonist and a selective estrogen receptor degrader (SERD), this mechanism of action provides complete blocking of the estrogen signaling pathway. In the FALCON phase III study (n = 462), which included postmenopausal MBC patients who had not previously received any endocrine therapy, fulvestrant 500 mg was compared with the aromatase inhibitor anastrozole. Significant improvement in PFS was achieved with fulvestrant therapy compared to anastrozole: 16.6 months in the fulvestrant group versus 13.8 months with anastrozole [OR = 0.797; 95% CI 0.637–0.999; P = 0.0486]. A subgroup analysis showed that patients without visceral metastases can benefit most from taking fulvestrant. In all studies fulvestrant 500 mg has demonstrated a good toxicity profile, so it is being studied as a component of combined endocrine therapy. In the PALOMA-3 study the combination of fulvestrant with palbociclib (CDK4/6 inhibitor) demonstrated a median PFS 9.5 months, compared with monotherapy with fulvestrant – 4.6 months (HR = 0.46, p < 0.0001). In the MONALEESA-3 study, the median PFS in patients receiving ribociclib with fulvestrant was significantly higher compared to those taking placebo with fulvestrant: 20.5 months and 12.8 months, respectively (HR = 0.593; 95% CI: 0.480–0.732; p < 0.001). In the MONARCH-2 study the combination of fulvestrant and abemaciclib was studied in the second line of therapy, the median PFS was 16.4 months in the group of fulvestrant and abemaciclib, and 9.3 months in the group of fulvestrant and placebo (HR = 0.553; 95% CI 0.449–0.681; p < 0.0001). The SOLAR-1 study demonstrated the efficacy of the combination of fulvestrant + alpelisib (PI3K inhibitor) in luminal HER2-negative mBC associated with PIK3CA mutation in the first and second lines of therapy. The median PFS in the fulvestrant + alpelisib group was 11 months compared with 5.7 months in the fulvestrant group (HR = 0.65; 95% CI 0.50–0.85; p < 0.001). Based on clinical research data, the combination of aromatase inhibitors with CDK4/6 inhibitors is the optimal first-line treatment in patients with hormone-sensitive tumors, i.e. with progression more than 1 year after the end of adjuvant hormone therapy. While fulvestrant ± CDK4/6 inhibitors is used for disease progression on the background of adjuvant hormone therapy in the first line or as a second line for progression on aromatase inhibitor therapy for metastatic cancer. The combination fulvestrant + alpelisib is highly effective in the second-line treatment of luminal HER2negative breast cancer in the presence of a PIK3CA mutation.

1. Каприн АД, Старинский ВВ, Петрова ГВ (ред.). Состояние онкологической помощи населению России в 2018 году. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2019. 236 с. Режим доступа: https://oncology-association.ru/wp-content/uploads/2020/09/sostoyanie_2018.pdf.

2. Miller K, Siegel R, Lin C, Mariotto A, Kramer J, Rowland J et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271–289. https://doi.org/10.3322/caac.21349.

3. Demicheli R, Dillekås H, Straume O, Biganzoli E. Distant metastasis dynamics following subsequent surgeries after primary breast cancer removal. Breast Cancer Res. 2019;21(1):57. https://doi.org/10.1186/s13058-019-1139-7.

4. Demicheli R, Abbattista A, Miceli R, Valagussa P, Bonadonna G. Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res Treat. 1996;41(2):177–185. https://doi.org/10.1007/BF01807163.

5. Demicheli R, Bonadonna G, Hrushesky WJ, Retsky M, Valagussa P. Menopausal status dependence of the timing of the breast cancer recurrence after surgical removal of the primary tumor. Breast Cancer Res. 2004;6(6):R689–696. https://doi.org/10.1186/bcr937.

6. Tyulyandin SA, Artamonova EV, Zhigulev AN, Zhukova AN, Koroleva IA, Parokonnaya AА et al. Breast cancer. Malignant Tumors. 2024;14(3s2-2):32–81. (In Russ.) https://doi.org/10.18027/2224-5057-2024-14-3s2-1.2-01.

7. Cleator SJ, Ahamed E, Coombes RC, Palmieri C. A 2009 update on the treatment of patients with hormone receptor-positive breast cancer. Clin Breast Cancer. 2009;9(1):6–17. https://doi.org/10.3816/CBC.2009.s.001.

8. Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, Matos L, Gelmon K, Aapro M et al. 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7). Breast. 2024;76:103756. https://doi.org/10.1016/j.breast.2024.103756.

9. Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine. Cochrane Database Syst Rev. 2003;2003(2):CD002747. https://doi.org/10.1002/14651858.CD002747.

10. Matthews J, Gustafsson JA. Estrogen signaling: a subtle balance between ER alpha and ER beta. Mol Interv. 2003;3(5):281–292. https://doi.org/10.1124/mi.3.5.281.

11. Ezdakov YаM, Gimaev IA, Tihonov DA. Review of modern representations on the structure and function of the estrogen receptors, their conformational changes in interaction with agonists and antagonists. Universum: Chemistry and Biology. 2017;(9):4–10. (In Russ.) Available at: http://7universum.com/ru/nature/archive/item/5083.

12. Smetnik AA. Estrogen receptors and their functions (literature review). Russian Journal of Human Reproduction. 2011;(3):31–37. (In Russ.)

13. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G et al. Human estrogen receptor b-gene structure,chromosomal localization and expression pattern. J Clin Endocrinol Metab. 1997;82(12):4258–4265. https://doi.org/10.1210/jcem.82.12.4470.

14. Klinge CM. Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res. 2001;29(14):2905–2919. https://doi.org/10.1093/nar/29.14.2905.

15. Moverare-Skrtic S, Borjesson AE, Farman HH, Sjögren K, Windahl S, Lagerquist M et al. The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor alpha AF-2 is modified. Proc Natl Acad Sci USA. 2014;111:1180–1185. https://doi.org/10.1073/pnas.1322910111.

16. Yaşar P, Ayaz G, User SD, Güpür G, Muyan M. Molecular mechanism of estrogen-estrogen receptor signaling. Reprod Med Biol. 2016;16(1):4–20. https://doi.org/10.1002/rmb2.12006.

17. Stanisić V, Lonard DM, O’Malley BW. Modulation of steroid hormone receptor activity. Prog Brain Res. 2010;181:153–176. https://doi.org/10.1016/S0079-6123(08)81009-6.

18. Ozturk S, Demir R. Particular functions of estrogen and progesterone in establishment of uterine receptivity and embryo implantation. Histol Histopathol. 2010;25(9):1215–1228. https://doi.org/10.14670/HH-25.1215.

19. Wenger CR, Beardslee S, Owens MA, Pounds G, Oldaker T, Vendely P et al. DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients. Breast Cancer Res Treat. 1993;28(1):9–20. https://doi.org/10.1007/BF00666351.

20. Simpson ER, Dowsett M. Aromatase and its inhibitors: significance for breast cancer therapy. Recent Prog Horm Res. 2002;57:317–338. https://doi.org/10.1210/rp.57.1.317.

21. Key TJ. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002;94(8):606–616. https://doi.org/10.1093/jnci/94.8.606.

22. Wakeling AE. Similarities and distinctions in the mode of action of different classes of antioestrogens. Endocr Relat Cancer. 2000;7(1):17–28. https://doi.org/10.1677/erc.0.0070017.

23. Powles TJ, Hickish T, Kanis JA, Tidy A, Ashleyet S. Effect of tamoxifen on bone mineral density measured by dual-energy X-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996;14(1):78–84. https://doi.org/10.1200/JCO.1996.14.1.78.

24. Fisher B, Constantino JP, Redmond CK, Fisher ER, Wickerham DL, Croninet WM. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 1994;86(7):527–537. https://doi.org/10.1093/jnci/86.7.527.

25. 25. Howell A. Preliminary experience with pure antiestrogens. Clin Cancer Res. 2001;7(Suppl. 12):4369s–4375s. Available at: https://pubmed.ncbi.nlm.nih.gov/11916227.

26. Wakeling AE, Bowler J. Steroidal pure antioestrogens. J Endocrinol. 1987;112(3):R7–R10. https://doi.org/10.1677/joe.0.112R007.

27. Fawell SE, White R, Hoare S, Sydenham M, Page M, Parker MG. Inhibition of estrogen receptor-DNA binding by the “pure” antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization. Proc Natl Acad Sci USA. 1990;87(17):6883–6887. https://doi.org/10.1073/pnas.87.17.6883.

28. Fan M, Rickert EL, Chen L, Aftab SA, Nephew KP, Weatherman RV. Characterization of molecular and structural determinants of selective estrogen receptor downregulators. Breast Cancer Res Treat. 2007;103(1):37–44. https://doi.org/10.1007/s10549-006-9353-2.

29. Nicholson RI, Gee JM, Manning DL, Wakeling AE, Montano MM, Katzenellenbogen BS. Responses to pure antiestrogens (ICI 164384, ICI 182780) in estrogen-sensitive and -resistant experimental and clinical breast cancer. Ann N Y Acad Sci. 1995;761:148–163. https://doi.org/10.1111/j.1749-6632.1995.tb31376.x.

30. Howell SJ, Johnston SR, Howell A. The use of selective estrogen receptor modulators and selective estrogen receptor down-regulators in breast cancer. Best Pract Res Clin Endocrinol Metab. 2004;18(1):47–66. https://doi.org/10.1016/j.beem.2003.08.002.

31. Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR еt al. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002;20(16):3396–3403. https://doi.org/10.1200/JCO.2002.10.057.

32. Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S et al. Doubleblind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 2002;20(16):3386–3395. https://doi.org/10.1200/JCO.2002.10.058.

33. Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer. 2003;98(2):229–238. https://doi.org/10.1002/cncr.11468.

34. Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M et al. Doubleblind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol. 2008;26(10):1664–1670. https://doi.org/10.1200/JCO.2007.13.5822.

35. McCormack P, Sapunar F. Pharmacokinetic profile of the fulvestrant loading dose regimen in postmenopausal women with hormone receptor–positive advanced breast cancer. Clin Breast Cancer. 2008;8(4):347–351. https://doi.org/10.3816/CBC.2008.n.040.

36. Ohno S, Rai Y, Iwata H, Yamamoto N, Yoshida M, Iwase H et al. Three dose regimens of fulvestrant in postmenopausal Japanese women with advanced breast cancer: results from a double-blind, phase II comparative study (FINDER1). Ann Oncol. 2010;21(12):2342–2347. https://doi.org/10.1093/annonc/mdq249.

37. Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010;28(30):4594–4600. https://doi.org/10.1200/JCO.2010.28.8415.

38. Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R et al. Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2014;106(1):djt337. https://doi.org/10.1093/jnci/djt337.

39. Robertson JF, Llombart-Cussac A, Rolski J, Feltl D, Dewar J, Macpherson E 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. https://doi.org/10.1200/JCO.2008.21.1136.

40. Robertson JF, Lindemann JP, Llombart-Cussac A, Rolski J, Feltl D, Dewar J et al. 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):503–511. https://doi.org/10.1007/s10549-012-2192-4.

41. Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiówka M, Hewson N 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. https://doi.org/10.1200/JCO.2015.61.5831.

42. Robertson JF, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptorpositive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016;388(10063):2997–3005. https://doi.org/10.1016/S0140-6736(16)32389-3.

43. Robertson JFR, Shao Z, Noguchi S, Bondarenko I, Panasci L, Singh S et al. Fulvestrant Versus Anastrozole in Endocrine Therapy-Naïve Women With Hormone Receptor-Positive Advanced Breast Cancer: Final Overall Survival in the Phase III FALCON Trial. J Clin Oncol. 2025;43(13):1539–1545. https://doi.org/10.1200/jco.24.00994.

44. Bross PF, Cohen MH, Williams GA, Pazdur R. FDA drug approval summaries: fulvestrant. Oncologist. 2002;7(6):477–480. https://doi.org/10.1634/theoncologist.7-6-477.

45. Vergote I, Robertson JF. Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials. Br J Cancer. 2004;90(Suppl. 1):S11– S14. https://doi.org/10.1038/sj.bjc.6601631.

46. Cheung KL, Robertson JF. Fulvestrant. Expert Opin Investig Drugs. 2002;11(2):303–308. https://doi.org/10.1517/13543784.11.2.303.

47. Bergh J, Jonsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattström D et al. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012;30(16):1919–1925. https://doi.org/10.1200/JCO.2011.38.1095.

48. Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L et al. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol. 2013;14(10):989–998. https://doi.org/10.1016/S1470-2045(13)70322-X.

49. Mehta RS, Barlow WE, Albain KS,Vandenberg TA, Dakhil SR, Tirumali NR et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012;367(5):435–444. https://doi.org/10.1056/NEJMoa1201622.

50. Turner NC, Ro J, Andre F. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373(17):1672–1673. https://doi.org/10.1056/NEJMoa1505270.

51. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N 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(7):e270. https://doi.org/10.1016/S1470-2045(15)00613-0.

52. Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA 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 Clin Oncol. 2018;36(24):2465–2472. https://doi.org/10.1200/JCO.2018.78.9909.

53. 53. Sledge GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X et al. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol. 2017;35(25):2875–2884. https://doi.org/10.1200/JCO.2017.73.7585.

54. Van Tine BA, Crowder RJ, Ellis MJ. ER and PI3K independently modulate endocrine resistance in ER-positive breast cancer. Cancer Discov. 2011;1(4):287–288. https://doi.org/10.1158/2159-8290.CD-11-0192.

55. Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S et al. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebocontrolled, phase 2 trial. Lancet Oncol. 2016;17(6):811–821. https://doi.org/10.1016/S1470-2045(16)00106-6.

56. Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(7):904–916. https://doi.org/10.1016/S1470-2045(17)30376-5.

57. Di Leo A, Seok Lee K, Ciruelos E, Lønning P, Janni W, O’Regan R et al. BELLE-3: a phase III study of buparlisib + fulvestrant in postmenopausal women with HR+, HER2-, aromatase inhibitor-treated, locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor-based treatment. Cancer Res. 2017;77(Suppl. 4):S4–S7. https://doi.org/10.1158/1538-7445.SABCS16-S4-07.

58. André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929–1940. https://doi.org/10.1056/NEJMoa1813904.

59. André F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021;32(2):208–217. https://doi.org/10.1016/j.annonc.2020.11.011.

60. Rugo HS, Lerebours F, Ciruelos E, Drullinsky P, Ruiz-Borrego M, Neven P et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptorpositive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021;22(4):489–498. https://doi.org/10.1016/S1470-2045(21)00034-6.

61. Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R. ESR1 mutations-a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol. 2015;12(10):573–583. https://doi.org/10.1038/nrclinonc.2015.117.

62. Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM et al. Emergence of constitutively active estrogen receptor-alpha mutations in pretreated advanced estrogen receptorpositive breast cancer. Clin Cancer Res. 2014;20(7):1757–1767. https://doi.org/10.1158/1078-0432.CCR-13-2332.

63. Fribbens C, O’Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34(25):2961–2968. https://doi.org/10.1200/JCO.2016.67.3061.

64. Turner NC, Swift C, Kilburn L, Fribbens C, Beaney M, Garcia-Murillas I et al. ESR1 Mutations and Overall Survival on Fulvestrant versus Exemestane in Advanced Hormone Receptor-Positive Breast Cancer: A Combined Analysis of the Phase III SoFEA and EFECT Trials. Clin Cancer Res. 2020;26(19):5172–5177. https://doi.org/10.1158/1078-0432.CCR-20-0224.

65. Bidard FC, Hardy-Bessard AC, Dalenc F, Bachelot T, Pierga JY, de la Motte Rouge T et al. PADA-1 investigators. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, openlabel, multicentre, phase 3 trial. Lancet Oncol. 2022;23(11):1367–1377. https://doi.org/10.1016/S1470-2045(22)00555-1.

66. Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M еt al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10):870–884. https://doi.org/10.1007/s12325-013-0060-1.

67. Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016;375(20):1925–1936. https://doi.org/10.1056/NEJMoa1607303.

68. Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptorpositive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904–915. https://doi.org/10.1016/S1470-2045(18)30292-4.

69. Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J at al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017;35(32):3638–3646. https://doi.org/10.1200/JCO.2017.75.6155.

70. Sonke GS, Van Ommen-Nijhof A, Wortelboer N, van der Noort V, Swinkels A, Blommestein H et al. Primary outcome analysis of the phase 3 SONIA trial (BOOG-2017-03) on selecting the optimal position of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in patients with hormone receptor positive, HER2-negative advanced breast cancer. J Clin Oncol. 2023;41(17_suppl):LBA1000-LBA1000. https://doi.org/10.1200/JCO.2023.41.17_suppl.LBA1000.