medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-202417-53-57medalphabet-3853Research ArticleДИАГНОСТИКА И ОНКОТЕРАПИЯDIAGNOSTICS AND ONCOTHERAPYНовая стратегия адъювантной терапии гормонозависимого HER2-негативного рака молочной железы: обновленные результаты исследования абемациклиба при ранних и местнораспространенных стадиях заболеванияNew treatment strategy for early hormone receptor-positive HER2-negative breast cancer: updated results of adjuvant abemaciclib trial in operable and locally advanced breast cancerhttps://orcid.org/0000-0001-5289-7866ТитоваТ. А.TitovaT. A.

Титова Татьяна Александровна - к.м.н., научный сотрудник отделения лекарственных методов лечения № 11

Москва

Titova Tatiana A.- PhD Med, researcher at Dept of Antitumor Drug Therapy No. 1

Moscow

tatiana.titovadoc@gmail.comhttps://orcid.org/0000-0001-7728-9533АртамоноваЕ. В.ArtamonovaE. V.

Артамонова Елена Владимировна - д.м.н., профессор, зав. отделением лекарственных методов лечения № 1; профессор кафедры онкологии и лучевой терапии; зав. кафедрой онкологии и торакальной хирургии

Москва

Artamonova Elena V. - DM Sci (habil.), head of Dept of Antitumor Drug Therapy No.1 Dept of Drug Treatment; professor at Dept of Oncology and Radiation Therapy; head of Dept of Oncology and Thoracic Surgery

Moscow

artamonovae@mail.ruФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National Medical Investigation Centre of OncologyRussian FederationФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава России; ФГАОУ ВО «Российский Национальный Исследовательский Медицинский Университет имени Н.И. Пирогова» Минздрава России, кафедра онкологии и лучевой терапии; ГБУЗ Московской области «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского», кафедра онкологии и торакальной хирургииРоссияN.N. Blokhin National Medical Investigation Centre of Oncology; Dept of Oncology and Radiation Therapy at N.I. Pirogov Russian National Research Medical University; Dept of Oncology and Thoracic Surgery at M. F. Vladimirsky Moscow Regional Research Clinical InstituteRussian Federation202408092024017«Диагностика и онкотерапия» (2)5357Copyright © Титова Т.А., Артамонова Е.В., 20242024Титова Т.А., Артамонова Е.В.Titova T.A., Artamonova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/3853

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

Abemaciclib is an oral inhibitor 4 and 6 (CDK4/6). Abemaciclib differs from other drugs in this group in suppression spectrum of cyclin-dependent kinases and is proven to improve survival rates in different treatment lines of metastatic breast cancer. In randomized clinical trials 3rd phase in patients with early hormone-dependent HR+ HER2 negative breast cancer high risk of progression abemaciclib in conjunction with hormone therapy significantly improves invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS). Long- term outcome studies monarchE with 5 – year follow – up of patients showed that abemaciclib adding to ET increases 5-year IDFS from 76 to 83.6% (HR0.680; 95% CI 0.599 to 0.772; p <0.001) and 5-year DRFS from 79.2% to 86.0% (HR0.675; 95% CI 0.588 to 0.774; p <0.001). Adverse events of 3rd degree and higher are registrated in 45.5% of patients in abemaciclib group and in 12,7% in control group and mainly presented by neutropenia (18.6 and 0.7%) and diarrhea (7,6 and 0.1%). Toxicity profile was expected and controlled. The reasonable dose reduction of abemaciclib did not lead to deterioration of long-term treatment result.

абемациклибранний рак молочной железыадъювантная терапиягормонотерапия: abemaciclibearly breast canceradjuvant therapyendocrine therapyReferencesSheffield 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.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.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.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.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.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.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.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.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.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.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/s41523–024–00639–1Matthew 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/s41523–024–00639–1Miguel 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/s10549–023–07002–1Miguel 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/s10549–023–07002–1Early 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)61074–1Early 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)61074–1Sledge 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.2017.73.7585Sledge 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.2017.73.7585Johnston 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-zJohnston 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-zSmith 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)30458–7Smith 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)30458–7Dickler 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-17–0754Dickler 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-17–0754Neil 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.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.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/cancers16091749O’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/cancers16091749Rocco 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 6Rocco 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 6Johnston 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.20.02514Johnston 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.20.02514Sung 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.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.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.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.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.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.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 9D’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

The authors declare that there are no conflicts of interest present.