Новая стратегия адъювантной терапии гормонозависимого HER2-негативного рака молочной железы: обновленные результаты исследования абемациклиба при ранних и местнораспространенных стадиях заболевания

Абемациклиб – пероральный ингибитор CDK4/6 – отличается по спектру подавления циклин-зависимых киназ от других препаратов этой группы и доказанно улучшает показатели выживаемости в различных линиях лечения метастатического рака молочной железы (мРМЖ). В рандомизированном клиническом исследовании (РКИ) III фазы у больных с ранним гормонозависимым HER2-негативным (Гр+ HER2-) раком молочной железы (РМЖ) с высоким риском прогрессирования абемациклиб в комбинации со стандартной адъювантной эндокринотерапией (АЭТ) значимо увеличивает выживаемость без инвазивного заболевания (ВБИЗ) и выживаемость без отдаленных метастазов (ВБОМ). Отдаленные результаты исследования monarchE с 5-летним сроком наблюдения за пациентками показали, что добавление абемациклиба к АГТ увеличивает 5-летнюю ВБИЗ с 76,0 до 83,6% (ОР=0,680; 95% ДИ 0,599–0,772; p<0,001) и 5-летнюю ВБОМ с 79,2 до 86,0%. (ОР=0,675; 95% ДИ 0,588–0,774; p<0,001). Нежелательные явления (НЯ) 3-й степени и выше отмечены у 45,5% пациентов на фоне терапии абемациклибом и у 12,7% в группе контроля и преимущественно представлены нейтропенией (18,6 и 0,7%) и диарей (7,6 и 0,1%). Профиль токсичности был ожидаемый и управляемый. Обоснованное снижение дозы абемациклиба не приводило к ухудшению отдаленных результатов лечения

1. Sheffield KM, Peachey JR, Method M. et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol. 2022;18: 2667–2682.

2. Johnston SRD, Toi M, O’Shaughnessy J. et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023; 24: 77–90.

3. Howell A, Cuzick J, Baum M. et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005; 365: 60–62.

4. Salvo EM, Ramirez AO, Cueto J. et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis. Breast. 2021; 57: 5–17.

5. Hamilton EP, Kim JH, Eigeliene N. et al: Efficacy and safety results by age in monarchE: Adjuvant abemaciclib combined with endocrine therapy (ET) in patients with HR+, HER2-node-positive, high-risk early breast cancer (EBC). J. Clin. Oncol. 2023; 41: 501.

6. Matthew P G, Irfan C, Laura T. et al. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study NPJ Breast Cancer. 2024 Apr 26; 10(1): 34. DOI: 10.1038/s41523–024–00639–1

7. Miguel M, Eva C., Álvaro R.L. Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry. Breast Cancer Research and Treatment. 2023; 201: 151–159. https://doi.org/10.1007/s10549–023–07002–1

8. Early Breast Cancer Trialists’ Collaborative Group (eBCTCG) Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015; 386: 1341–1352. DOI: 10.1016/S0140–6736(15)61074–1

9. Sledge G.W., Toi M., Neven P., Sohn J., Inoue K., Pivot X. 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: 2875–2884. DOI: 10.1200/JCO.2017.73.7585

10. Johnston S., Martin M., Di Leo A., Im S.A., Awada A., Forrester T. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Canc. 2019; 5: 5. DOI: 10.1038/s41523–018–0097-z

11. Smith I., Robertson J., Kilburn L., Wilcox M., Evans A., Holcombe C. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020; 21: 1443–1454. DOI: 10.1016/S1470–2045(20)30458–7

12. Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR(+)/HER2(–) metastatic breast cancer. Clin. Cancer. Res. 2017; 23: 5218–5224. DOI: 10.1158/1078–0432.CCR-17–0754

13. Neil O., Dylan C., Richard B. et al. Preclinical Activity of Abemaciclib Alone or in CombiMCT-17–0290 nation with Antimitotic and Targeted Therapies in Breast Cancer. DOI: 10.1158/1535–7163.

14. O’Connor, T.N.; Schultz, E.; Wang, J. et al. Real-World Experience among Elderly Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitor-Based Therapy. Cancers 2024; 16: 1749. https://doi.org/10.3390/cancers16091749

15. Rocco N, Ghilli M, Curcio A, Bortul M. et al. Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC). Eur. J. Surg. Oncol. 2024 Feb; 50 (2): 107954. DOI: 10.1016/j.ejso.2024.107954. Epub 2024 Jan 6

16. Johnston S., Harbeck N., Hegg R. et al. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR1, HER22, Node-Positive, High-Risk, Early Breast Cancer (monarchE) J. Clin. Oncol. 38: 3987–3998. DOI https://doi.org/10.1200/JCO.20.02514

17. 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: 209–249.

18. Salvo EM, Ramirez AO, Cueto J. et al. Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis. Breast. 2021; 57: 5–17.

19. Di Cosimo S, Porcu L, Cardoso F. CDK 4/6 inhibitors mired in uncertainty in HR positive and HER2 negative early breast cancer. Breast. 2021; 55: 75–78.

20. D’Onofrio R., Sperduti I., Piacentini F. et al. Thromboembolism and Adjuvant Endocrine Therapy (AET) in Hormone Receptor-Positive Early Breast Cancer (EBC): Did Treatment Evolution Change Incidence of the Adverse Event? A Meta-Analysis. Clin. Breast. Cancer. 2023 Dec; 23 (8): e534–e541. DOI: 10.1016/j.clbc.2023.09.002. Epub 2023 Sep 9