The ICEDORA study: clinical and demographic characteristics and treatment regimens of patients with HR+ HER2- locally advanced or metastatic breast cancer receiving CDK4/6 inhibitors in real clinical practice

   Introduction. CDK4/6 inhibitors in combination with endocrine therapy (ET) are the current standard of care for patients with HR+ HER2- advanced and metastatic breast cancer (eBC and mBC). Evidence of the clinical efficacy of CDK4/6 inhibitors has been obtained in several randomized clinical trials (RCTs), but data on their efficacy in real-world clinical practice (RCP) are contradictory.

   Objective. The aim of the ICEDORA study was to analyze clinical and demographic characteristics, treatment regimens, and clinical outcomes in patients with HR+ HER2- mBC and mBC receiving CDK4/6 inhibitors in a real-world clinical practice in Moscow.

   Materials and methods. ICEDORA is a non-interventional retrospective study based on the analysis of data on patients receiving CDK 4/6 inhibitors in Moscow. Clinical characteristics and treatment details of all patients with HR+ HER2-breast cancer who received ribociclib, palbociclib, or abemaciclib from January 2020 to the end of December 2022 were extracted from primary medical records (outpatient charts and medical histories) by parsing. Overall survival (OS) was calculated from the date of breast cancer diagnosis until patient death using the Kaplan-Meier method, and differences between treatment groups were assessed using the log-rank test. Multivariate logistic regression and Cox proportional hazards models were built to exclude the influence of confounders and systematic errors.

   Results. The analysis included 2051 patients. 58.7 % received palbociclib, 34.7 % — ribociclib, 6.6 % — abemaciclib. The median age in the overall population was 58 years, but it was higher in the abemaciclib group (62 years). In 83.5 % of cases, Her2/neu was negative, the groups were homogeneous in this indicator. The level of estrogen receptors (ER) Ki-67 was significantly higher in the abemaciclib group. In the overall population, patients with primary metastatic breast cancer (stage IV) accounted for 42.1 %. The distribution of stages within each group was comparable. The groups differed significantly in the number of metastases due to a higher proportion of patients with one metastasis in the abemaciclib group (31.9 %) compared to the ribociclib (19.0 %) and palbociclib (16.6 %) groups, where the number of metastatic foci was more than one. Comorbidity was present in 90 % of patients. Differences in the baseline characteristics of patients receiving different drugs require caution when interpreting the study results.

   Conclusion. The ICEDORA study, which included patients taking CDK4/6 inhibitors in real-world clinical practice in Moscow, is one of the largest analyses of clinical and demographic characteristics, treatment regimens, and clinical outcomes in patients with HR+ HER2- mBC and mBC taking CDK4/6 inhibitors in real-life clinical practice in Russia. Comparative analysis of the efficacy of ribociclib, palbociclib, and abemaciclib in real-life clinical practice was not planned or conducted due to differences in the clinical and demographic characteristics of patients. Larger multicenter data with
balanced cohorts and long-term follow-up are needed.

1. The state of oncological care for the population of Russia in 2023. Edited by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow: P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Center of Radiology of the Ministry of Health of the Russian Federation, 2022. – ill. – 262 p. (In Russ.)

2. Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. 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. doi: 10.1016/S1470-2045(15)00613-0

3. Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. 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. doi: 10.1200/JCO.2017.73.7585

4. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O'Shaughnessy J. Updated results from MONALEESA-2, a phase III 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. doi: 10.1093/annonc/mdy155

5. Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. 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. doi: 10.1016/S1470-2045(18)30292-4

6. Rugo HS, Finn RS, Diéras V, Ettl J, Lipatov O, Joy AA, Harbeck N, Castrellon A, Iyer S, Lu DR, Mori A, Gauthier ER, Bartlett CH, Gelmon KA, Slamon DJ. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat. 2019;174(3):719-729. doi: 10.1007/s10549-018-05125-4

7. Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Sondhi M, Wang Y, Chakravartty A, Rodriguez-Lorenc K, Taran T, Jerusalem G. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2020;382:514-524. doi: 10.1056/NEJMoa1911149

8. Johnston S, O'Shaughnessy J, Martin M, Huober J, Toi M, Sohn J, André VAM, Martin HR, Hardebeck MC, Goetz MP. Abemaciclib as initial therapy for advanced breast cancer: MONARCH 3 up-dated results in prognostic subgroups. NPJ Breast Cancer. 2021;22;7(1):80. doi: 10.1038/s41523-021-00289-7

9. Abdallah HMA, Owoseni YI, Sultan A, Ahmed S, Wood J, Varadhan B, Ayodele O. 448P Real-world experience with CDK4/6 inhibitors for HR+/HER2-metastatic breast cancer (MBC). Ann Oncol. 2023;34(2):S369-S370. doi: 10.1016/j.annonc.2023.09.624

10. Miron AI, Anghel AV, Barnonschi AA, Mitre R, Liscu HD, Găinariu E, Pătru R, Coniac S. Real-World Outcomes of CDK4/6 Inhibitors Treatment in Metastatic Breast Cancer in Romania. Diagnostics (Basel). 2023;13(11):1938. doi: 10.3390/diagnostics13111938

11. Chen BF, Tsai YF, Chao TC, Lien PJ, Lin YS, Feng CJ, Chen YJ, Cheng HF, Liu CY, Lai JI, Tseng LM, Huang CC. Real-world experience with CDK4/6 inhibitors in hormone receptor-positive metastatic and recurrent breast cancer: findings from an Asian population. Clin Exp Med. 2024;24(1):185. doi: 10.1007/s10238-024-01458-1

12. Gehrchen ML, Berg T, Garly R, Jensen MB, Eßer-Naumann S, Rønlev JD, Nielsen HM, Knoop A, Kümler I. Real-world effectiveness of CDK 4/6 inhibitors in estrogen-positive metastatic breast cancer. BJC Rep. 2024;2(1):44. doi: 10.1038/s44276-024-00070-w

13. Plavetic ND, Čular K, Gudelj D, Kaceljak K, Križić M, Popovic M, Bulimbašić S, Sirotković-Skerlev M, Bubanović S, Silovski T. Real-world comparison of the efficacy of three CDK4/6 inhibitors (CDK4/6i) in the first-line treatment of endocrine-sensitive advanced breast cancer (aBC): Single institution experience. J Clin Oncol. 2024;42(16):e13080-e13080. doi: 10.1200/JCO.2024.42.16_suppl.e13080

14. Patel R, Mathews J, Hamm C, Kulkarni S, Gupta R, Opperman T, Chiong JD, Nasser A. Real-World Experience with CDK4/6 Inhibitors in the first-line palliative setting for HR+/HER2- advanced breast cancer. Curr Oncol. 2025;32(1):52. doi: 10.3390/curroncol32010052

15. Rugo HS, Layman RM, Lynce F, Liu X, Li B, McRoy L, Cohen AB, Estevez M, Curigliano G, Brufsky A. Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2- metastatic breast cancer in the US real-world setting. ESMO Open. 2025;10(1):104103 doi: 10.1016/j.esmoop.2024.104103

16. Clinical guidelines of the Ministry of Health of Russia. Breast Cancer. 2021. (In Russ.) https://oncology-association.ru/wp-content/uploads/2021/02/rak-molochnoj-zhelezy-2021.pdf

17. Tyulyandin SA, Artamonova EV, Zhigulev AN, Zhukova LG, Koroleva IA, Parokonnaya AA, Semiglazova TYu, Stenina MB, Frolova MA. Breast cancer. RUSSCO practical recommendations, part 1.2. Malignant tumors. 2024;14(3s2):32–81. (In Russ.)

18. Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, Matos L, Gelmon K, Aapro MS, Bajpai J, Barrios CH, Bergh J, Bergsten-Nordström E, Biganzoli L, Cardoso MJ, Carey LA, Chavez-MacGregor M, Chidebe R, Cortés J, Curigliano G, Dent RA, El Saghir NS, Eniu A, Fallowfield L, Francis PA, Franco Millan SX, Gilchrist J, Gligorov J, Gradishar WJ, Haidinger R, Harbeck N, Hu X, Kaur R, Kiely B, Kim SB, Koppikar S, Kuper-Hommel MJJ, Lecouvet FE, Mason G, Mertz SA, Mueller V, Myerson C, Neciosup S, Offersen BV, Ohno S, Pagani O, Partridge AH, Penault-Llorca F, Prat A, Rugo HS, Senkus E, Sledge GW, Swain SM, Thomssen C, Vorobiof DA, Vuylsteke P, Wiseman T, Xu B, Costa A, Norton L, Winer EP. 6^th and 7^ер International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7). The Breast. 2024;76:103756. doi: 10.1016/j.breast.2024.103756

19. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Breast Cancer Version 3.2025 Invasive Breast Cancer. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

20. Gold standard for prevention, diagnosis, treatment and rehabilitation of patients with breast cancer 2025. (In Russ.) https://docs.google.com/document/d/14XU19rSHmmg0v8aL9msY9B1uoscVK7WS/edit#heading=h.gjdgxs

21. Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Conte P, Lu Y, Barriga S, Hurt K, Frenzel M, Johnston S, Llombart-Cussac A. 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. doi: 10.1001/jamaoncol.2019.4782

22. Cristofanilli M, Rugo HS, Im SA, Slamon DJ, Harbeck N, Bondarenko I, Masuda N, Colleoni M, DeMichele A, Loi S, Iwata H, O'Leary B, André F, Loibl S, Bananis E, Liu Y, Huang X, Kim S, Lechuga Frean MJ, Turner NC. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021;39:15_suppl:1000-1000. doi: 10.1200/JCO.2021.39.15_suppl.1000

23. Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte PF, Cameron D, André F, Arteaga C, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J. Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32(suppl_5):S1283-S1346. doi: 10.1016/annonc/annonc741

24. Tripathy D, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Vazquez RV, Jung KH, Babu KG; Wheatley-Price P, De Laurentiis M, Im Y-H, Kümmel S, El-Saghir N, Liu M-C, Kaur S, Gasch C, Wang C, Wang Y, Chakravartty A, Luet Y-S. 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. Cancer Res. 2021;81(4_Suppl):PD2-04. doi: 10.1158/1538-7445.SABCS20-PD2-04

25. Finn RS, Rugo HS, Dieraset VC, Harbeck N, Im S-A, Gelmon KA, Walshe JM, Martin M, Mac Gregor MC, Bananis E, Gauthier ERd, Lu DR, Kim S, Slamon DJ. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. J Clin Oncol. 2022;40(17_suppl):LBA1003. doi: 10.1200/JCO.2022.40.17_suppl.LBA1003

26. Goetz MP, Toi M, Huober J, Sohn J, Trédan O, Park IH, Campone M, Chen SC, Manso LM, Paluch-Shimon S, Freedman OC, O'Shaughnessy J, Pivot X, Tolaney SM, Hurvitz SA, Llombart-Cussac A, André V, Saha A, van Hal G, Shahir A, Iwata H, Johnston SRD. Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3. Ann Oncol. 2024;35(8):718-727. doi: 10.1016/j.annonc.2024.04.013

27. Slamon DJ, Diéras V, Rugo HS, Harbeck N, Im SA, Gelmon KA, Lipatov ON, Walshe JM, Martin M, Chavez-MacGregor M, Bananis E, Gauthier E, Lu DR, Kim S, Finn RS. Overall survival with palbociclib plus letrozole in advanced breast cancer. J Clin Oncol. 2024;42(9):994-1000. doi: 10.1200/JCO.23.00137

28. State Register of Medicines. (In Russ.) https://grls.rosminzdrav.ru/default.aspx