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Новые возможности терапии гормоноположительного HER2-отрицательного метастатического рака молочной железы с альтерациями сигнального пути АКТ. Резолюция совета экспертов
Новые возможности терапии гормоноположительного HER2-отрицательного метастатического рака молочной железы с альтерациями сигнального пути AKT. Резолюция совета экспертов. Современная Онкология. 2024;26(3):262–268. DOI: 10.26442/18151434.2024.3.203012
© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.
© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.
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New therapies for hormone-positive HER2-negative metastatic breast cancer with AKT signaling alterations: the Expert Panel Decision. Journal of Modern Oncology. 2024;26(3):262–268. DOI: 10.26442/18151434.2024.3.203012
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Аннотация
20 мая 2024 г. в г. Москве в рамках совета экспертов состоялось обсуждение ключевых вопросов диагностики альтераций сигнального пути AKT, эффективности и безопасности таргетной терапии гормоноположительного (HR+) HER2-отрицательного метастатического рака молочной железы (РМЖ) в связи с появлением нового селективного ингибитора AKT – капивасертиба. Представлены результаты исследования CAPItello-291. Экспертами сделан вывод о том, что в арсенале онкологов появилась новая эффективная линия лечения больных гормонорезистентным распространенным гормоноположительным HER2-отрицательным РМЖ с наличием генетических альтераций в сигнальном пути AKT, с развитием рецидива на предшествующей адъювантной эндокринотерапии ингибиторами ароматазы или в течение первого года после ее окончания либо с прогрессированием во время предшествующей терапии ингибиторами ароматазы по поводу метастатического РМЖ. Современные методы генетического тестирования на наличие альтераций в сигнальном пути AKT позволят подтвердить наличие в опухоли данной ключевой биологической мишени для назначения эффективной таргетной терапии.
Ключевые слова: метастатический рак молочной железы, распространенный рак молочной железы, гормонорезистентный рак молочной железы, селективный ингибитор AKT, таргетная терапия, капивасертиб
Ключевые слова: метастатический рак молочной железы, распространенный рак молочной железы, гормонорезистентный рак молочной железы, селективный ингибитор AKT, таргетная терапия, капивасертиб
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On May 20, 2024, the Expert Panel discussed key issues of the diagnosis of alterations of the AKT signaling pathway, the effectiveness and safety of targeted therapy for hormone-positive (HR+) HER2-negative metastatic breast cancer (BC) concerning the emergence of a new selective AKT inhibitor capivasertib. The results of the CAPItello-291 study are presented. The experts concluded that a new effective treatment line has become available for patients with hormone-resistant advanced hormone-positive HER2-negative BC with genetic alterations in the AKT signaling pathway and relapse on previous adjuvant endocrine therapy with aromatase inhibitors or within the first year after the therapy or with progression during previous therapy with aromatase inhibitors for metastatic BC. Modern genetic testing methods for the alterations in the AKT signaling pathway can confirm the presence of this key biological target in the tumor for tailoring effective targeted therapy.
Keywords: metastatic breast cancer, advanced breast cancer, hormone-resistant breast cancer, selective AKT inhibitor, targeted therapy, capivasertib
Полный текст
Список литературы
1. Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5). DOI:10.1093/jnci/dju055
2. Тюляндин С.А., Артамонова Е.В., Жигулев А.Н., и др. Практические рекомендации по лекарственному лечению рака молочной железы. Практические рекомендации RUSSCO #3s2, часть 1. Злокачественные опухоли. 2023;13:157-200 [Tiuliandin SA, Artamonova EV, Zhigulev AN, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu raka molochnoi zhelezy. Prakticheskie rekomendatsii RUSSCO #3s2, chast' 1. Zlokachestvennye opukholi. 2023;13:157-200 (in Russian)]. DOI:10.18027/2224-5057-2023-13-3s2-1-157-200
3. Huang J, Zheng L, Sun Z, Li J. CDK4/6 inhibitor resistance mechanisms and treatment strategies (Review). Int J Mol Med. 2022;50(4). DOI:10.3892/ijmm.2022.5184
4. Millis SZ, Ikeda S, Reddy S, et al. Landscape of Phosphatidylinositol-3-Kinase Pathway Alterations Across 19 784 Diverse Solid Tumors. JAMA Oncol. 2016;2(12):1565-53. DOI:10.1001/jamaoncol.2016.0891
5. O'Leary B, Cutts RJ, Liu Y, et al. The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial. Cancer Discov. 2018;8(11):1390-403. DOI:10.1158/2159-8290.CD-18-0264
6. Wander SA, Cohen O, Gong X, et al. The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor-Positive Metastatic Breast Cancer. Cancer Discov. 2020;10(8):1174-13. DOI:10.1158/2159-8290.CD-19-1390
7. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023;388(22):2058-70. DOI:10.1056/NEJMoa2214131
8. Ma CX, Reinert T, Chmielewska I, Ellis MJ. Mechanisms of aromatase inhibitor resistance. Nat Rev Cancer. 2015;15(5):261-75. DOI:10.1038/nrc3920
9. Pereira B, Chin SF, Rueda OM, et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun. 2016;7:11479. DOI:10.1038/ncomms11479
10. Frogne T, Jepsen JS, Larsen SS, et al. Antiestrogen-resistant human breast cancer cells require activated protein kinase B/Akt for growth. Endocr Relat Cancer. 2005;12(3):599-614. DOI:10.1677/erc.1.00946
11. Miller TW, Hennessy BT, González-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010;120(7):2406-13. DOI:10.1172/JCI41680
12. Wang Q, Chen X, Hay N. Akt as a target for cancer therapy: more is not always better (lessons from studies in mice). Br J Cancer. 2017;117(2):159-63. DOI:10.1038/bjc.2017.153
13. Andrikopoulou A, Chatzinikolaou S, Panourgias E, et al. The emerging role of capivasertib in breast cancer. Breast. 2022;63:157-67. DOI:10.1016/j.breast.2022.03.018
14. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive 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):489-98. DOI:10.1016/S1470-2045(21)00034-6
15. Davies BR, Greenwood H, Dudley P, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther. 2012;11(4):873-7. DOI:10.1158/1535-7163.MCT-11-0824-T
16. Ribas R, Pancholi S, Guest SK, et al. AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo. Mol Cancer Ther. 2015;14(9):2035-48. DOI:10.1158/1535-7163.MCT-15-0143
17. Jones RH, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020;21(3):345-57. DOI:10.1016/S1470-2045(19)30817-4
18. Howell SJ, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol. 2022;23(7):851-64. DOI:10.1016/S1470-2045(22)00284-4
19. Rugo HS. Capivasertib and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2- advanced breast cancer (ABC): Second progression-free survival (PFS2) and time to first subsequent chemotherapy (TFSC) in the CAPItello-291 trial. Annals of Oncology. 2024;9(suppl. 4):1-47.
2. Тюляндин С.А., Артамонова Е.В., Жигулев А.Н., и др. Практические рекомендации по лекарственному лечению рака молочной железы. Практические рекомендации RUSSCO #3s2, часть 1. Злокачественные опухоли. 2023;13:157-200 [Tiuliandin SA, Artamonova EV, Zhigulev AN, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu raka molochnoi zhelezy. Prakticheskie rekomendatsii RUSSCO #3s2, chast' 1. Zlokachestvennye opukholi. 2023;13:157-200 (in Russian)]. DOI:10.18027/2224-5057-2023-13-3s2-1-157-200
3. Huang J, Zheng L, Sun Z, Li J. CDK4/6 inhibitor resistance mechanisms and treatment strategies (Review). Int J Mol Med. 2022;50(4). DOI:10.3892/ijmm.2022.5184
4. Millis SZ, Ikeda S, Reddy S, et al. Landscape of Phosphatidylinositol-3-Kinase Pathway Alterations Across 19 784 Diverse Solid Tumors. JAMA Oncol. 2016;2(12):1565-53. DOI:10.1001/jamaoncol.2016.0891
5. O'Leary B, Cutts RJ, Liu Y, et al. The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial. Cancer Discov. 2018;8(11):1390-403. DOI:10.1158/2159-8290.CD-18-0264
6. Wander SA, Cohen O, Gong X, et al. The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor-Positive Metastatic Breast Cancer. Cancer Discov. 2020;10(8):1174-13. DOI:10.1158/2159-8290.CD-19-1390
7. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023;388(22):2058-70. DOI:10.1056/NEJMoa2214131
8. Ma CX, Reinert T, Chmielewska I, Ellis MJ. Mechanisms of aromatase inhibitor resistance. Nat Rev Cancer. 2015;15(5):261-75. DOI:10.1038/nrc3920
9. Pereira B, Chin SF, Rueda OM, et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun. 2016;7:11479. DOI:10.1038/ncomms11479
10. Frogne T, Jepsen JS, Larsen SS, et al. Antiestrogen-resistant human breast cancer cells require activated protein kinase B/Akt for growth. Endocr Relat Cancer. 2005;12(3):599-614. DOI:10.1677/erc.1.00946
11. Miller TW, Hennessy BT, González-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010;120(7):2406-13. DOI:10.1172/JCI41680
12. Wang Q, Chen X, Hay N. Akt as a target for cancer therapy: more is not always better (lessons from studies in mice). Br J Cancer. 2017;117(2):159-63. DOI:10.1038/bjc.2017.153
13. Andrikopoulou A, Chatzinikolaou S, Panourgias E, et al. The emerging role of capivasertib in breast cancer. Breast. 2022;63:157-67. DOI:10.1016/j.breast.2022.03.018
14. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive 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):489-98. DOI:10.1016/S1470-2045(21)00034-6
15. Davies BR, Greenwood H, Dudley P, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther. 2012;11(4):873-7. DOI:10.1158/1535-7163.MCT-11-0824-T
16. Ribas R, Pancholi S, Guest SK, et al. AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo. Mol Cancer Ther. 2015;14(9):2035-48. DOI:10.1158/1535-7163.MCT-15-0143
17. Jones RH, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020;21(3):345-57. DOI:10.1016/S1470-2045(19)30817-4
18. Howell SJ, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol. 2022;23(7):851-64. DOI:10.1016/S1470-2045(22)00284-4
19. Rugo HS. Capivasertib and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2- advanced breast cancer (ABC): Second progression-free survival (PFS2) and time to first subsequent chemotherapy (TFSC) in the CAPItello-291 trial. Annals of Oncology. 2024;9(suppl. 4):1-47.
________________________________________________
1. Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5). DOI:10.1093/jnci/dju055
2. Tiuliandin SA, Artamonova EV, Zhigulev AN, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu raka molochnoi zhelezy. Prakticheskie rekomendatsii RUSSCO #3s2, chast' 1. Zlokachestvennye opukholi. 2023;13:157-200 (in Russian). DOI:10.18027/2224-5057-2023-13-3s2-1-157-200
3. Huang J, Zheng L, Sun Z, Li J. CDK4/6 inhibitor resistance mechanisms and treatment strategies (Review). Int J Mol Med. 2022;50(4). DOI:10.3892/ijmm.2022.5184
4. Millis SZ, Ikeda S, Reddy S, et al. Landscape of Phosphatidylinositol-3-Kinase Pathway Alterations Across 19 784 Diverse Solid Tumors. JAMA Oncol. 2016;2(12):1565-53. DOI:10.1001/jamaoncol.2016.0891
5. O'Leary B, Cutts RJ, Liu Y, et al. The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial. Cancer Discov. 2018;8(11):1390-403. DOI:10.1158/2159-8290.CD-18-0264
6. Wander SA, Cohen O, Gong X, et al. The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor-Positive Metastatic Breast Cancer. Cancer Discov. 2020;10(8):1174-13. DOI:10.1158/2159-8290.CD-19-1390
7. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023;388(22):2058-70. DOI:10.1056/NEJMoa2214131
8. Ma CX, Reinert T, Chmielewska I, Ellis MJ. Mechanisms of aromatase inhibitor resistance. Nat Rev Cancer. 2015;15(5):261-75. DOI:10.1038/nrc3920
9. Pereira B, Chin SF, Rueda OM, et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun. 2016;7:11479. DOI:10.1038/ncomms11479
10. Frogne T, Jepsen JS, Larsen SS, et al. Antiestrogen-resistant human breast cancer cells require activated protein kinase B/Akt for growth. Endocr Relat Cancer. 2005;12(3):599-614. DOI:10.1677/erc.1.00946
11. Miller TW, Hennessy BT, González-Angulo AM, et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J Clin Invest. 2010;120(7):2406-13. DOI:10.1172/JCI41680
12. Wang Q, Chen X, Hay N. Akt as a target for cancer therapy: more is not always better (lessons from studies in mice). Br J Cancer. 2017;117(2):159-63. DOI:10.1038/bjc.2017.153
13. Andrikopoulou A, Chatzinikolaou S, Panourgias E, et al. The emerging role of capivasertib in breast cancer. Breast. 2022;63:157-67. DOI:10.1016/j.breast.2022.03.018
14. Rugo HS, Lerebours F, Ciruelos E, et al. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive 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):489-98. DOI:10.1016/S1470-2045(21)00034-6
15. Davies BR, Greenwood H, Dudley P, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther. 2012;11(4):873-7. DOI:10.1158/1535-7163.MCT-11-0824-T
16. Ribas R, Pancholi S, Guest SK, et al. AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo. Mol Cancer Ther. 2015;14(9):2035-48. DOI:10.1158/1535-7163.MCT-15-0143
17. Jones RH, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020;21(3):345-57. DOI:10.1016/S1470-2045(19)30817-4
18. Howell SJ, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol. 2022;23(7):851-64. DOI:10.1016/S1470-2045(22)00284-4
19. Rugo HS. Capivasertib and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2- advanced breast cancer (ABC): Second progression-free survival (PFS2) and time to first subsequent chemotherapy (TFSC) in the CAPItello-291 trial. Annals of Oncology. 2024;9(suppl. 4):1-47.
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