Revisiones en Cáncer 00025 / http://dx.doi.org/10.20960/revcancer.00025
Resumen| PDF

Revisión

Más allá de la primera línea del cáncer del mama metastásico HER2+


Carmen Salvador-Coloma

Prepublicado: 2023-07-12
Publicado: 2023-07-17

Logo Descargas   Número de descargas: 29513      Logo Visitas   Número de visitas: 1170      Citas   Citas: 0

Compártelo:


El cáncer de mama HER2 positivo es uno de los tumores más agresivos. Se han desarrollado muchos agentes terapéuticos nuevos que permiten una importante mejoría en el pronóstico de estas pacientes. En primera línea, el estándar de tratamiento continúa siendo el doble bloqueo asociado a un taxano. Recientemente, los conjugados anticuerpo-fármaco de nueva generación han dado lugar a unos resultados sin precedentes, y se ha establecido el trastuzumab deruxtecán como un nuevo estándar en segunda línea. A pesar de los avances en el desarrollo terapéutico, la mayoría de las pacientes presentan resistencias y finalmente recaen. La esperanza de vida disminuye con cada línea adicional de tratamiento. En respuesta a esta necesidad, se están explorando nuevos mecanismos, agentes dirigidos y combinaciones de fármacos que tratan de modificar la historia natural del cáncer de mama metastásico HER2 positivo.

Palabras Clave: Cáncer de mama metastásico. HER2 positivo. Segunda línea de tratamiento. Tratamiento dirigido. Trastuzumab. Anticuerpos conjugados.



Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, et al. Cancer incidence and survival trends by subtype using data from the surveillance epidemiology and end results program, 1992–2013. Cancer Epidemiol Biomarkers Prev. 2017; 26(4): 632–41.
DOI: 10.1158/1055-9965.EPI-16-0520
Maria Gion, Dario Trapani, Alfonso Cortés, Carmine Valenza, Nancy Lin, Javier Cortés, and Giuseppe Curigliano. Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Moving Into a New Era. American Society of Clinical Oncology Educational Book 2022 :42, 82-92
DOI: 10.1200/EDBK_351222
Slamon DJ, Leyland-jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783-92.
DOI: 10.1056/NEJM200103153441101
Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014;32:3744-52.
DOI: 10.1200/JCO.2014.55.5730
Escrivá-de-Romaní E, Saura C. The change of paradigm in the treatment of HER2-positive breast cancer with the development of new generation antibody-drug conjugates. Cancer Drug Resist 2023;6:45-58.
DOI: 10.20517/cdr.2022.52
Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol 2007;18:977-84.
DOI: 10.1093/annonc/mdl475
Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol. 2010;28(1):92.
DOI: 10.1200/JCO.2008.19.9844
Balduzzi S, Mantarro S, Guarneri V, Tagliabue L, Pistotti V, Moja L, D'Amico R. Trastuzumab-containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2014.
DOI: 10.1002/14651858.CD006242.pub2
Metzger-Filho O, Winer EP, Krop I. Pertuzumab: optimizing HER2 blockade. Clin Cancer Res 2013;19:5552-6.
DOI: 10.1158/1078-0432.CCR-13-0518
Swain SM, Miles D, Kim S, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cáncer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 2020;21:519-30.
DOI: 10.1016/S1470-2045(19)30863-0
Vega Cano, K.S.; Marmolejo Castañeda, D.H.; Escrivá-de-Romaní, S.; Saura, C. Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends. Cancers 2023, 15,51.
DOI: 10.3390/cancers15010051
Anne F Schott, MD. Systemic treatment for HER2-positive metastatic breast cáncer. UpToDate. last updated: Jan 18, 2023. www.uptodate.com.
DOI: 10.1097/01.ASM.0000921968.31670.b5
Hafeez, U.; Parakh, S.; Gan, H.K.; Scott, A.M. Antibody-Drug Conjugates for Cancer Therapy. Molecules 2020, 25, 4764.
DOI: 10.3390/molecules25204764
Kalim, M.; Chen, J.; Wang, S.; Lin, C.; Ullah, S.; Liang, K.; Ding, Q.; Chen, S.; Zhan, J.B. Intracellular trafficking of new anticancer therapeutics: Antibody–drug conjugates. Drug Des. Dev. Ther. 2017, 11, 2265–2276.
Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387:9-20
DOI: 10.1056/NEJMoa2203690
Christoph Suppan, Marija Balic. Current Standards and Future Outlooks in Metastatic Her2-Positive Breast Cancer. Breast Care 2023;18:69–75.
DOI: 10.1159/000528756
Li L, Zhang D, Liu B, et al. Antibody-drug conjugates in HER2-positive breast cancer. Chin Med J 2021;135:261-7
DOI: 10.1097/CM9.0000000000001932
Nakada, T.; Sugihara, K.; Jikoh, T.; Abe, Y.; Agatsuma, T. The Latest Research and Development into the Antibody–Drug Conjugate, [fam-] Trastuzumab Deruxtecan (DS-8201a), for HER2 Cancer Therapy. Chem. Pharm. Bull. 2019, 67, 173–185.
Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res 2016;22:5097-108
DOI: 10.1158/1078-0432.CCR-15-2822
Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20(6): 816–26.
DOI: 10.1016/S1470-2045(19)30097-X
Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2020;382:610-21
DOI: 10.1056/NEJMoa1914510
Modi S, Saura C, Yamashita T, et al. Updated results from DESTINY-Breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd) in HER2-positive metastatic breast cancer. San Antonio Breast Cancer Symposium; 2020.
DOI: 10.21037/tbcr-21-20
Cort_es J, Kim S-B, Chung W-P, et al; DESTINY-Breast03 Trial Investigators. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154
DOI: 10.1056/NEJMoa2115022
Hamilton, E.P.; Bragaia, V.P.; Yeo, W.; Kim, S.B.; Bianchini, G.; Yamashita, T.; Yonemori, K.; Inoue, K.; Curigliano, G.; Hurvitz, S.; et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) vs. trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. J. Clin. Oncol. 2021, 40, 1000.
Pérez-García, J.M.; Vaz-Batista, M.; Cortez, P.; Ruiz-Borrego, M.; Cejalvo, J.M.; de la Haba-Rodriguez, J.; Garrigós, L.; Racca, F.; Servitja, S.; Blanch, S.; et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial. Neuro Oncol. 2022; Online ahead of print.
DOI: 10.1093/neuonc/noac144
Bartsch, R.; Berghoff, A.S.; Furtner, J.; Marhold, M.; Bergen, E.S.; Roider-Schur, S.; Starzer, A.M.; Forstner, H.; Rottenmanner, B.; Dieckmann, K.; et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: A single-arm, phase 2 trial. Nat. Med. 2022, 8, 1840–1847.
DESTINY-Breast12 trial (ClinicalTrials.gov Identifier: NCT04739761). Phase .3. A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer (DESTINY-B12)
Gennari A, André F, Barrios CH, et al; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol 2021;32:1475-95.
DOI: 10.1016/j.annonc.2021.09.019
Highlights of prescribing information: Enhertu (fam-trastuzumab deruxtecan-nxki). US Food and Drug Administration. Available at: https://www.accessdata.fda.gov
Andre, F.; Hamilton, E.P.; Loi, S.; Schmid, P.; Anders, C.K.; Yu, T.; Boston, S.; D’Cruz, C.M.; Herbolsheimer, P.; Jhaveri, K.L. Trastuzumab deruxtecan (T-DXd) combinations in patients with HER2-positive advanced or metastatic breast cancer: A phase 1b/2, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast07). J. Clin. Oncol. 2021, 39 (Suppl. S15), TPS1096
DOI: 10.1200/JCO.2021.39.15_suppl.TPS1096
Tolaney, S.M.; Barroso-Sousa, R.; Jiang, Z.; Park, Y.H.; Rimawi, M.; Saura, C.; Schneeweiss, A.; Toi, M.; Yu, T.; Shetty, J.; et al. 328TiP Phase III study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09. Ann. Oncol. 2021, 32, S507–S508
DOI: 10.1016/j.annonc.2021.08.611
A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05. ClinicalTrials.gov Identifier: NCT04622319
S Mano M. Trastuzumab emtansine: a game changer in HER2-positive early breast cancer. Future Oncol. 2020; 16(32): 2595–609.
DOI: 10.2217/fon-2020-0219
Erickson HK, Park PU, Widdison WC, et al. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 2006;66:4426-33
DOI: 10.1158/0008-5472.CAN-05-4489
Mittendorf EA, Wu Y, Scaltriti M, et al. Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 2009;15:7381-8.
DOI: 10.1158/1078-0432.CCR-09-1735
Sakai H, Tsurutani J, Iwasa T, et al. HER2 genomic amplification in circulating tumor DNA and estrogen receptor positivity predict primary resistance to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. Breast Cancer 2018;25:605-13
DOI: 10.1007/s12282-018-0861-9
Filho OM, Viale G, Stein S, et al. Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab. Cancer Discov 2021;11:2474-8
DOI: 10.1158/2159-8290.CD-20-1557
Trail PA, Dubowchik GM, Lowinger TB. Antibody drug conjugates for treatment of breast cancer: novel targets and diverse approaches in ADC design. Pharmacol Ther 2018;181:126-42
DOI: 10.1016/j.pharmthera.2017.07.013
Verma S, Miles D, Gianni L, et al; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367:1783-9
DOI: 10.1056/NEJMoa1209124
Diéras, V.; Miles, D.; Verma, S.; Pegram, M.;Welslau, M.; Baselga, J.; Krop, I.E.; Blackwell, K.; Hoersch, S.; Xu, J.; et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): A descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017, 18, 732–742
Krop, I.E.; Kim, S.B.; González-Martín, A.; LoRusso, P.M.; Ferrero, J.M.; Smitt, M.; Yu, R.; Leung, A.C.;Wildiers, H.; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): A randomised, open-label, phase 3 trial. Lancet Oncol. 2014, 15, 689–699.
Krop, I.E.; Kim, S.B.; Martin, A.G.; LoRusso, P.M.; Ferrero, J.M.; Badovinac-Crnjevic, T.; Hoersch, S.; Smitt, M.; Wildiers, H. Trastuzumab emtansine versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): Final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017, 18, 743–754.
Perez EA, Barrios C, Eiermann W, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer 2019;125:3974- 84.
DOI: 10.1002/cncr.32392
Hurvitz SA, Martin M, Jung KH, et al. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase III KRISTINE study. J Clin Oncol 2019;37:2206 16.
DOI: 10.1200/JCO.19.00882
Von Minckwitz G, Huang CS, Mano MS, et al; KATHERINE Investigators. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380:617-28
DOI: 10.1056/NEJMoa1814017
Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2020; 382:597.
DOI: 10.1056/NEJMoa1914609
Curigliano G, Mueller V, Borges V, et al. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol. 2022;33:321-329.
DOI: 10.1016/j.annonc.2021.12.005
Lin, N.U.; Borges, V.; Anders, C.; Murthy, R.K.; Paplomata, E.; Hamilton, E.; Hurvitz, S.; Loi, S.; Okines, A.; Abramson, V.; et al. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J. Clin. Oncol. 2020, 38, 2610–2619.
Saura C, Oliveira M, Feng Y-H, et al; NALA Investigators. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA Trial. J Clin Oncol. 2020;38:3138-3149.
DOI: 10.1200/JCO.20.00147
Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010; 15(9): 924–34
DOI: 10.1634/theoncologist.2009-0181
Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012; 30(21): 2585–92.
DOI: 10.1200/JCO.2011.35.6725
Johnston S, Pippen J Jr., Pivot X, Lichinitser M, Sadeghi S, Dieras V, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009; 27(33): 5538–46.
DOI: 10.1200/JCO.2009.23.3734
Xu, B.; Yan, M.; Ma, F.; Hu, X.; Feng, J.; Ouyang, Q.; Tong, Z.; Li, H.; Zhang, Q.; Sun, T.; et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): A multicentre, open-label, randomized, controlled, phase 3 trial. Lancet Oncol. 2021, 22, 351–360.
Rugo HS, Im SA, Cardoso F, et al; SOPHIA Study Group. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. 2021;7:573-584
DOI: 10.1001/jamaoncol.2020.7932
Saura Manich C, O’Shaughnessy J, Aftimos PG, et al. LBA15 primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer. Ann Oncol. 2021;32:S1288.
DOI: 10.1016/j.annonc.2021.08.2088
Rimawi M, Ferrero J-M, de la Haba-Rodriguez J, et al; PERTAIN Study Group. First-line trastuzumab plus an aromatase inhibitor, with or without pertuzumab, in human epidermal growth factor receptor 2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (PERTAIN): a randomized, open-label phase II trial. J Clin Oncol. 2018;36:2826-2835
DOI: 10.1200/JCO.2017.76.7863
Johnston SRD, Hegg R, Im SA, et al. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: updated results of ALTERNATIVE. J Clin Oncol. 2021;39:79-89
DOI: 10.1200/JCO.20.01894
Tolaney SM, Wardley AM, Zambelli S, Hilton JF, Troso-Sandoval TA, Ricci F, et al. Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard of care chemotherapy in women with hormone hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial. Lancet Oncol. 2020; 21(6): 763–75.
DOI: 10.1016/S1470-2045(20)30112-1
Loi S, Giobbie-Hurder A, Gombos A, et al; International Breast Cancer Study Group, the Breast International Group. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol. 2019;20:371-382.
DOI: 10.1016/S1470-2045(18)30812-X
Huober J, Barrios CH, Niikura N, et al. VP6-2021: IMpassion050: A phase III study of neoadjuvant atezolizumab + pertuzumab + trastuzumab + chemotherapy (neoadj A + PH + CT) in high-risk, HER2-positive early breast cancer (EBC). Ann Oncol. 2021;32:1061-1062.
DOI: 10.1016/j.annonc.2021.05.800

Revisión: Posibilidades terapéuticas para el cáncer de mama avanzado HER2-low

Alfonso López de Sá Lorenzo

Revisión: Primera línea de tratamiento sistémico del cáncer de mama metastásico triple negativo

Julia Tejerina Peces , Fernando Moreno Antón

Revisión: Terapia neoadyuvante en cáncer localmente avanzado de mama HER2 positivo

Publicado: 2023-03-29 / http://dx.doi.org/

Revisión: Tratamiento del cáncer de mama luminal tras inhibidores de ciclo celular

Rodrigo Sánchez Bayona , Manuel Alva Bianchi

Revisión: Tratamiento del cáncer de mama metastásico hormonosensible en primera línea

Ignacio Chacón López-Muñiz , Juan David Cárdenas , Irene Otero Blas

Revisión: Cáncer de mama triple negativo: segunda y sucesivas líneas de tratamiento

Fernando Henao Carrasco , Sara Leal Sánchez

Revisión: Primera línea de tratamiento paliativo del cáncer de mama HER2+

Patricia Pérez de Aguado Rodríguez , Víctor Alía Navarro , Noelia Martínez Jáñez

Revisión: Líneas de investigación clínica en el tratamiento del cáncer de próstata

Carlos González Merino , Marta Viana Aragonés , José Miguel Rodellar Sanz , Víctor Albarrán Fernández , Teresa Alonso Gordoa

Artículos más populares

Revisión: Principios del cáncer de próstata resistente a la castración

El cáncer de próstata resistente a la castración (...

Publicado: 2024-02-08

Revisión: Inmunoterapia en el tratamiento del cáncer de próstata

El cáncer de próstata es la segunda neoplasia en v...

Publicado: 2023-12-03

Revisión: PET y radionúclidos en cáncer de próstata

En la actualidad se dispone de múltiples radiotraz...

Publicado: 2024-01-04

Una cookie o galleta informática es un pequeño archivo de información que se guarda en su navegador cada vez que visita nuestra página web. La utilidad de las cookies es guardar el historial de su actividad en nuestra página web, de manera que, cuando la visite nuevamente, ésta pueda identificarle y configurar el contenido de la misma en base a sus hábitos de navegación, identidad y preferencias. Las cookies pueden ser aceptadas, rechazadas, bloqueadas y borradas, según desee. Ello podrá hacerlo mediante las opciones disponibles en la presente ventana o a través de la configuración de su navegador, según el caso. En caso de que rechace las cookies no podremos asegurarle el correcto funcionamiento de las distintas funcionalidades de nuestra página web. Más información en el apartado “POLÍTICA DE COOKIES” de nuestra página web.