SEOM recomienda la aprobación del uso de Pertuzumab en combinación con quimioterapia y trastuzumab en pacientes con cáncer de mama HER2 positivo en estadios precoces y con características de alto riesgo, definidas por la presencia de ganglios positivos. En las pacientes que hayan recibido Pertuzumab como tratamiento
neoadyuvante, si se opta por su utilización como tratamiento adyuvante, deben completarse un total 18 ciclos de tratamiento con Pertuzumab y trastuzumab, independientemente del momento de la intervención o de la respuesta al tratamiento, pero se considera incierto el beneficio de su uso en las pacientes que tras neoadyuvancia han obtenido una respuesta completa patológica.
No hay actualmente evidencia suficiente para seleccionar su uso de acuerdo a otros criterios clínicos o a biomarcadores. Los datos en tumores con receptores hormonales negativos no se consideran suficientemente claros para recomendar el fármaco en pacientes de dicho grupo que no tengan a la vez afectación ganglionar.
La indicación del tratamiento debe realizarse con una comprensión adecuada por la paciente de la magnitud del beneficio, de su balance con la toxicidad y de la incertidumbre con respecto a su impacto a largo plazo. Es también fundamental que la determinación de HER2 sea realizada con procedimientos validados y de acuerdo a criterios de consenso internacionales, en centros con una política de calidad activa para su realización.
8. BIBLIOGRAFÍA
1 von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med 2017; 377: 122–131.
2 EMA. CHMP extension of indication variation assessment report: Perjeta (Procedure No. EMEA/H/C/002547/II/0034). 2018.
3 Grove A, Andronis L, Gallacher D, Nduka C, Court R, Vepa A et al. Single technology appraisal pertuzumab for adjuvant treatment of HER2-positive early breast cancer (ID1192): A Single Technology Appraisal. Warwick Evidence, 2018. 2018.
4 NICE. NICE: Pertuzumab for adjuvant treatment of early HER2 positive breast cancer (ID1192). Public project documents (acceso el 20-Agosto-2018). 2018. 5 Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M et al. Adjuvant
Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011; 365: 1273–1283. 6 Denduluri N, Chavez-MacGregor M, Telli ML, Eisen A, Graff SL, Hassett MJ et al.
Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update. J Clin Oncol 2018; 36: 2433–2443.
Version 3.2018-October 2018. 2018.
8 AGO Breast Commitee. Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer. Recommendations 2018. 2018.
9 Curigliano G, Burstein HJ, Winer EP, Gnant M, Dubsky P, Loibl S et al. De-
escalating and escalating treatments for early-stage breast cancer: The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol 2017; 28: 1700–1712.
10 Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016. doi:10.1016/S1470-2045(15)00551-3.
11 Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5- year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18: 1688–1700.
12 Cherny NI, Sullivan R, Dafni U, Kerst JM, Sobrero A, Zielinski C et al. A
standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol Off J Eur Soc Med Oncol 2016. doi:10.1093/annonc/mdw258.
13 Cherny NI, Dafni U, Bogaerts J, Latino NJ, Pentheroudakis G, Douillard J-Y et al. ESMO-Magnitude of Clinical Benefit Scale version 1.1. Ann Oncol 2017; 28: 2340– 2366.
14 Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018; : NEJMoa1804710.
15 Martín M, Ruiz A, Borrego MR, Barnadas A, González S, Calvo L et al. Fluorouracil, Doxorubicin, and Cyclophosphamide (FAC) Versus FAC Followed by Weekly Paclitaxel As Adjuvant Therapy for High-Risk, Node-Negative Breast Cancer: Results From the GEICAM/2003-02 Study. J Clin Oncol 2013; 31: 2593–2599. 16 Shulman LN, Berry DA, Cirrincione CT, Becker HP, P EA, O’R R et al.
Comparison of Doxorubicin and Cyclophosphamide Versus Single-Agent Paclitaxel As Adjuvant Therapy for Breast Cancer in Women With 0 to 3 Positive Axillary Nodes: CALGB 40101 (Alliance). J Clin Oncol 2014; 32: 2311–2317.
17 Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E et al. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med 2010; 363: 2200–10.
18 Mackey JR, Martin M, Pienkowski T, Rolski J, Guastalla J-P, Sami A et al. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10- year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol 2013; 14: 72–80.
19 EBCTG. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341–1352.
20 Dafni U, Karlis D, Pedeli X, Bogaerts J, Pentheroudakis G, Tabernero J et al. Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules. ESMO Open 2017; 2: e000216.
21 Del Paggio JC, Sullivan R, Schrag D, Hopman WM, Azariah B, Pramesh CS et al. Delivery of meaningful cancer care: a retrospective cohort study assessing cost and benefit with the ASCO and ESMO frameworks. Lancet Oncol 2017; 18: 887–894.
Methodological approach to determine minor, considerable, and major treatment effects in the early benefit assessment of new drugs. Biometrical J 2016; 58: 43–58. 23 Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja
E et al. 11 y ’ f w-up of trastuzumab after adjuvant chemotherapy in HER2- positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet (London, England) 2017; 389: 1195–1205.
24 Slamon D, Eiermann W, Robert N, et al. Slamon DJ, Eiermann W, Robert NJ, et al. Ten year follow-up of the BCIRG-006 trial comparing doxorubicin plus
cyclophosphamide followed by docetaxel (AC-T) with doxorubicin plus
cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel. Cancer Res 2015; 76: S5-04.
25 Perez EA, Romond EH, Suman VJ, Jeong J-H, Sledge G, Geyer CE 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.
26 Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E et al. 11 y ’ f w-up of trastuzumab after adjuvant chemotherapy in HER2- positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 2017; 389: 1195–1205.
27 Bulbul A, Araujo-Mino E, Dayao ZR. The Conundrum of Adjuvant HER2 Treatment Options. Front Oncol 2018; 8: 177.
28 Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N et al. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol 2017; 18: 545–554.
29 Cejalvo JM, Pascual T, Fernández-Martínez A, Brasó-Maristany F, Gomis RR, Perou CM et al. Clinical implications of the non-luminal intrinsic subtypes in hormone receptor-positive breast cancer. Cancer Treat Rev 2018; 67: 63–70. 30 Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R et al. Pertuzumab
plus trastuzumab in combination with standard neoadjuvant anthracycline-
containing and anthracycline-free chemotherapy regimens in patients with HER2- positive early breast cancer: a randomized phase II cardiac safety study
(TRYPHAENA). Ann Oncol Off J Eur Soc Med Oncol 2013; 24: 2278–84.
31 Gianni L, Pienkowski T, Im Y-H, Roman L, Tseng L-M, Liu M-C et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25–32.
32 Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): A phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol 2018; 29: 646–653.
33 Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N et al.
Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; pii: S0140-6736(13)62422–8.
34 Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M et al. Long- term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant
anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer 2018; 89: 27–35.
35 Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced,
inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a
multicentre, open-label, phase 2 randomised trial. Lancet Oncol 2016; 17: 791–800. 36 López-Fernández T, Martín García A, Santaballa Beltrán A, Montero Luis Á, García
Sanz R, Mazón Ramos P et al. Cardio-Onco-Hematología en la práctica clínica. Documento de consenso y recomendaciones. Rev Española Cardiol 2017; 70: 474– 486.