Therapie des fortgeschrittenen hormonrezeptor(HR)-positiven HER2-negativen Mammakarzinoms

Zusammenfassung

Der Artikel gibt einen Überblick über die aktuellen Therapieoptionen des metastasierten hormonrezeptorpositiven und HER2-negativen Mammakarzinoms. Im Fokus stehen Kombinationstherapien z. B. mit CDK4/6-Inhibition im Vergleich zu rein endokrin basierten Therapien in Prä- und Postmenopause mit Darlegung der neuesten Studienergebnisse. Die Hinzunahme eines CDK4/6-Inhibitors zu einer endokrin basierten Therapie mit Aromataseinhibitor oder Fulvestrant führt zu einer deutlichen Verbesserung des progressionsfreien Überlebens und ist vorteilhaft unabhängig davon, ob es sich um Palbociclib, Ribociclib oder Abemaciclib handelt. Der daher besondere klinische Stellenwert der Inhibition cyclinabhängiger Kinasen spricht für den Einsatz in der Erstlinienbehandlung von Frauen mit metastasiertem, hormonrezeptorpositivem und HER2-negativem Mammakarzinom im Vergleich zu den verfügbaren rein endokrin basierten Therapien.

Abstract

The article gives an overview of current treatment options for metastatic hormone receptor-positive and HER2-negative breast cancer. The focus is on combined therapies, e. g., with CDK4/6 inhibition compared with purely endocrine-based therapies in the pre- and postmenopause, presenting the latest study results. The addition of a CDK4/6 inhibitor to endocrine-based therapy with an aromatase inhibitor or fulvestrant leads to a marked improvement in progression-free survival and is independently beneficial whether palbociclib, ribociclib or abemaciclib is involved. The particular clinical status of inhibition of cyclin-dependent kinases argues for its use in the first-line treatment of women with metastatic, hormone receptor-positive and HER2-negative breast cancer compared with the available purely endocrine-based therapies.

Schlüsselwörter

Mammakarzinom - Metastasierung - hormonrezeptorpositiv - HER2‑negativ - CDK4/6‑Inhibitor

Key words

breast cancer - metastasis - hormone receptor‑positive - HER2‑negative - CDK4/6 inhibitor

• Literatur

• 1 Ervik E, Lam F, Ferlay J. et al Cancer Today. Lyon, France: International Agency for Research on Cancer; 2016 Online (Stand: 28.08.2019): http://gco.iarc.fr/today
• 2 Blows FM, Driver KE, Schmidt MK. et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med 2010; 7: e1000279
• 3 Ibrahim T, Farolfi A, Scarpi E. et al. Hormonal receptor, human epeidermal growth factor-2, and Ki67 discordance between primary breast cancer and paired metastases: clinical impact. Oncology 2013; 84: 150-157
• 4 Lindström LS, Karlsson E, Wilking UM. et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 2012; 30: 2601-2608
• 5 Rugo HS, Rumble RB, Macrae E. et al. Endocrine therapy for hormone-receptor-positive metastatic breast cancer. American Society of Clinical Oncology Guideline. J Clin Oncol 2016; 34: 3069-3103
• 6 Harbeck N, Gnant M. Breast Cancer. Lancet 2017; 389: 1134-1150
• 7 Bosseti C, Bertuccio P, Malvezzi M. et al. Cancer mortality in Europe, 2005–2009, and an overview of trends since 1980. Ann Oncol 2013; 24: 2657-2671
• 8 Jackisch C. Metastasiertes Mammakarzinom: Längeres und besseres Überleben. Dtsch Arztebl 2014; 111: 18
• 9 Cardoso F, Senkus E, Costa A. et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)†. Ann Oncol 2018; 29: 1634-1657
• 10 Ettl J, Harbeck H. The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Expert Rev Anticancer Ther 2017; 17: 661-668
• 11 Reinert T, Barrios CH. Overall survival and progression-free survival with endocrine therapy for hormone receptor-positive, HER2-negative advanced breast cancer: review. Ther Adv Med Oncol 2017; 9: 693-709
• 12 Wöckel A, Festl J, Stüber T. et al Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer. Geburtsh Frauenheilk 2018; 78: 927-948 . doi:10.1055/a-0646-4522
• 13 Thill M, Liedtke C, Müller V. et al AGO Breast Committee. AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2018. Breast Care (Basel) 2018; 13: 209-215 . doi:10.1159/000489331
• 14 Sledge jr GW, Hu P, Falkson G. et al. Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormonesensitive breast cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 2000; 18: 262-266
• 15 Thill M, Schmidt M. Management of adverse events during cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based treatment in breast cancer. Ther Adv Med Oncol 2018; 10: 1758835918793326 . doi:10.1177/1758835918793326
• 16 Robertson JFR, Bondarenko IM, Trishkina E. et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet 2016; 388: 2997-3005
• 17 Echavarria I, Jerez Y, Martin M. et al. Incorporating CDK4/6 Inhibitors in the Treatment of Advanced Luminal Breast Cancer. Breast Care (Basel) 2017; 12: 296-302
• 18 VanArsdale T, Bischoff C, Arndt KT. et al. Molecular pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. AACR Annual Meeting 2015. Clin Cancer Res 2015; 21: 2905-2910
• 19 Finn RS, Crown JP, Lang I. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015; 16: 25-35
• 20 Loibl S, Turner NC, Ro J. et al. Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 results. Oncologist 2017; 22: 1028-1038
• 21 Turner NC, Slamon DC, Ro J. et al. Overall survival with Palbociclib and Fulvestrant in advanced breast cancer. N Engl J Med 2018;
• 22 Hortobagyi GN, Stemmer SM, Burris HA. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016; 375: 1738-1748
• 23 Slamon DJ, Neven P, Cjia S. et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. MONALEESA-3. J Clin Oncol 2018; 36: 2465-2472
• 24 Goetz MP, Toi M, Campone M. et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017; 35: 3638-3646
• 25 Sledge jr GW, Toi M, Neven P. et al. MONARCH2: 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
• 26 Robertson JFR, Di Leo A, Fazal M. et al. Fulvestrant for hormone receptorpositive advanced breast cancer in patients with visceral versus non-visceral metastases: Findings from FALCON, FIRST and CONFIRM. San Antonio, TX: San Antonio Breast Cancer Symposium; 2017: PD5-09
• 27 Bergh J, Jönsson PE, Lidbrink EK. et al FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptorpositive postmenopausal breast cancer. J Clin Oncol 2012; 30: 1919-1925 . doi:10.1200/JCO.2011.38.1095
• 28 Mehta RS, Barlow WE, Albain KS. et al Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med 2012; 367: 435-444 . doi:10.1056/NEJMoa1201622
• 29 Finn RS, Martin M, Rugo HS. et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med 2016; 375: 1925-1936
• 30 Turner NC, Ro J, André F. et al PALOMA3 Study Group. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209-219 . doi:10.1056/NEJMoa1505270
• 31 Tripathy D, Im S, Colleoni M. et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol 2018; 19: 904-915
• 32 Klijn JG, Blamey R, Boccardo F. et al. Combined hormone agents Trialists Group and the European Organization for Reasearch and Treatment of Cancer. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol 2001; 19: 343-353
• 33 Hurvitz SA, Im SA, Lu YS. et al Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: overall survival (OS) results. J Clin Oncol 2019; 37 (Suppl.): Abstr. LBA1008 . doi:10.1200/JCO.2019.37.18_suppl.LBA1008
• 34 Lopez-Knowles E, OʼToole SA, McNeil CM. et al. PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer specific mortality. Int J Cancer 2010; 126: 1121-1131
• 35 Bachelot T, Bourgier C, Cropet C. et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol 2012; 30: 2718-2724
• 36 Baselga J, Campone M, Piccart M. et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366: 520-529
• 37 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG), Davies C, Godwin J et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771-784
• 38 Coleman RE, Bolten WW, Lansdown M. et al. Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev 2008; 34: 275-282
• 39 Dieras V, Rugo HS, Schnell P. et al. Long-term pooled safety analysis of Palbociclib in combination with endocrine therapy for HR+/HER2-advanced breast cancer. J Natl Cancer Inst 2018;
• 40 Durairaj C, Ruir-Garcia A, Gauthier ER. et al. Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer. Anticancer Drugs 2018; 29: 271-280
• 41 Tolaney SM, Lin NU, Thornton D. et al. Abemaciclib for the treatment of brain metastases (BM) secondary to hormone receptor positive (HR+), HER2 negative breast cancer. J Clin Oncol 2017; 35 (15) Abstr. 1019
• 42 Park YH, Kim TY, Kim GM. et al. A randomized phase II study of palbociclib plus exemestane with GnRH agonist versus capecitabine in premenopausal women with hormone receptor-positive metastatic breast cancer (KCSG‑BR 15-10, NCT02592746). J Clin Oncol 2019; 37: Abstr. 1007
• 43 Lobbezoo DJ, van Kampen RJ, Voogd AC. et al In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium. Ann Oncol 2016; 27: 256-262 . doi:10.1093/annonc/mdv544
• 44 Kolberg HC, Schneeweiss A, Fehm TN. et al. Update Breast Cancer 2019 Part 3 – Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel. Geburtsh Frauenheilk 2019; 79: 470-482
• 45 Wöckel A, Festl J, Stüber T. et al. Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer. Geburtsh Frauenheilk 2018; 78: 927-948