Update Mammakarzinom 2020 Teil 2 – fortgeschrittenes Mammakarzinom: neue Substanzen und Einzug diagnostikabhängiger Therapien

Zusammenfassung

Für Patientinnen mit einem lokal fortgeschrittenen bzw. metastasierten Mammakarzinom wurden in den letzten Jahren neue und effektive Therapien wie CDK4/6-Inhibitoren, PARP-Inhibitoren und ein PD-L1-Inhibitor eingeführt. In dieser Übersichtsarbeit wird ein Update zu den vorhandenen Studien mit ihrer Datenlage gegeben. Ebenso werden 2 innovative Anti-HER2-Therapien dargestellt (Trastuzumab-Deruxtecan und Tucatinib), für die die Ergebnisse aus neue Studien berichtet worden sind. Molekulare Tests bieten die Möglichkeit, Patientinnenpopulationen zu definieren oder auch Therapieverläufe zu monitorieren. Dieses kann helfen, Patientinnen mit spezifischen Eigenschaften zu identifizieren, um diesen eine individuelle zielgerichtete Therapie im Rahmen von Studien zukommen zu lassen. In einer großen Studie konnte der Nutzen einer solchen Biomarkerstudie zum ersten Mal beschrieben werden.

Schlüsselwörter

fortgeschrittenes Mammakarzinom - Metastasen - Therapie - Mutationstestung - Immuntherapie - PARP - CDK4/6 - BRCA1/2 - PD-L1

• References/Literatur

• 1 Im SA, Lu YS, Bardia A. et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019;
• 2 Slamon DJ, Neven P, Chia 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;
• 3 Slamon DJ, Neven P, Chia S. et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med 2019;
• 4 Sledge GW, Toi M, Neven P. et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol 2019;
• 5 Litton JK, Rugo HS, Ettl J. et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753-763
• 6 Robson M, Im S-A, Senkus E. et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523-533
• 7 Andre F, Ciruelos E, Rubovszky G. et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2019; 380: 1929-1940
• 8 Nakada T, Sugihara K, Jikoh T. et al. The Latest Research and Development into the Antibody-Drug Conjugate, [fam-] Trastuzumab Deruxtecan (DS-8201a), for HER2 Cancer Therapy. Chem Pharm Bull (Tokyo) 2019; 67: 173-185
• 9 Xu Z, Guo D, Jiang Z. et al. Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem 2019; 183: 111682
• 10 Tamura K, Tsurutani J, Takahashi S. 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: 816-826
• 11 Modi S, Saura C, Yamashita T. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med 2019;
• 12 Murthy RK, Loi S, Okines A. et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2019;
• 13 Murthy R, Borges VF, Conlin A. et al. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol 2018; 19: 880-888
• 14 Rugo HS, Im S-A, Cardoso F. et al. Phase 3 SOPHIA study of margetuximab + chemotherapy vs. trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: second interim overall survival analysis. San Antonio Breast Cancer Symposium 2019; 2019: GS1-02
• 15 Schmid P, Adams S, Rugo HS. et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018; 379: 2108-2121
• 16 Schmid P, Rugo HS, Adams S. et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2020; 21: 44-59
• 17 Chen H, Wu J, Zhang Z. et al. Association Between BRCA Status and Triple-Negative Breast Cancer: A Meta-Analysis. Front Pharmacol 2018; 9: 909
• 18 Fasching P, Hu C, Hart S. et al. Cancer predisposition genes in metastatic breast cancer – Association with metastatic pattern, prognosis, patient and tumor characteristics. Cancer Res 2018; 78: PD1-02 doi:10.1158/1538-7445.SABCS17-PD1-02
• 19 Diéras V, Han HS, Kaufman B. et al. Phase 3 study of veliparib with carboplatin and paclitaxel in HER2-negative advanced/metastatic gBRCA-associated breast cancer: BROCADE3. Ann Oncol 2019; 30 (Suppl. 05) v851-v934 doi:10.1093/annonc/mdz1394
• 20 Martín M, Zielinski C, Ruíz-Borrego M. et al. Results from PEARL study (GEICAM/2013-02_CECOG/BC.1.3.006): A phase 3 trial of Palbociclib (PAL) in combination with endocrine therapy (ET) versus Capecitabine (CAPE) in hormonal receptor (HR)-positive/human epidermal growth factor receptor (HER) 2-negative metastatic breast cancer (MBC) patients (pts) whose disease progressed on aromatase inhibitors (AIs). San Antonio Breast Cancer Symposium 2019; 2019: GS2-07
• 21 Dowsett M, Sestak I, Regan MM. et al. Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5. J Clin Oncol 2018; 36: 1941-1948
• 22 Cuzick J, Sestak I, Baum M. et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 2010; 11: 1135-1141
• 23 Regan MM, Francis PA, Pagani O. et al. Absolute improvements in freedom from distant recurrence with adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) HER2-negative breast cancer (BC): Results from TEXT and SOFT. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 503
• 24 Sparano JA, Gray RJ, Makower DF. et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018; 379: 111-121
• 25 Sestak I, Crager M, Cuzick J. et al. Validation of the clinical treatment score post 5 years (CTS5) in women with hormone receptor positive, HER2-negative, node-negative disease from the TAILORx study. San Antonio Breast Cancer Symposium 2019; 2019: GS4-03
• 26 King TA, Liu M, McClure MB. et al. Multiplatform analysis of matched primary and metastatic breast tumors from the AURORA US Network. San Antonio Breast Cancer Symposium 2019; 2019: GS3-08
• 27 Radovich M, Jiang G, Chitambar C. et al. Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy is significantly associated with disease recurrence in early-stage triple-negative breast cancer (TNBC): Preplanned correlative results from clinical trial BRE12-158. San Antonio Breast Cancer Symposium 2019; 2019: GS5-02
• 28 Turner N, Kingston B, Kilburn L. et al. Results from the plasmaMATCH trial: A multiple parallel cohort, multi-centre clinical trial of circulating tumour DNA testing to direct targeted therapies in patients with advanced breast cancer (CRUK/15/010). San Antonio Breast Cancer Symposium 2019; 2019: GS3-06
• 29 Kingston B, Bye H, Hubank M. et al. The genomic landscape of breast cancer based on ctDNA analysis: data from the plasmaMATCH trial. San Antonio Breast Cancer Symposium 2019; 2019: GS3-07
• 30 Mobus V, Jackisch C, Luck HJ. et al. Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial. Ann Oncol 2018; 29: 178-185
• 31 Blackley EF, Kesper MG, Savas P. et al. Long-term incidence of taxane induced peripheral neuropathy in early breast cancer patients, a real world, single centre experience exploring effects on health related quality of life. San Antonio Breast Cancer Symposium 2019; 2019: P1-17-06
• 32 Ditsch N, Untch M, Thill M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019. Breast Care (Basel) 2019; 14: 224-245
• 33 Leonard RCF, Mansi J, Yellowlees A. et al. Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial. San Antonio Breast Cancer Symposium 2019; 2019: P2-12-11
• 34 Etaix E, Zheng Y, Rosenberg S. et al. Fertility concerns and treatment decision-making among young women with breast cancer. San Antonio Breast Cancer Symposium 2019; 2019: P2-13-17
• 35 Centers for Medicare & Medicaid Services. Measure Refinements Report for Dry Run: Admissions and Emergency Department (ED) Visits for Patients Receiving Outpatient Chemotherapy. 2017. Online: https://cmit.cms.gov/CMIT_public/ReportMeasure?measureRevisionId=672 last access: 01.04.2020
• 36 Schilling J, Busch S, Stefek A. et al. Quality of life data of breast cancer patients receiving a fixed combination of netupitant/palonosetron (NEPA) for prevention of chemotherapy-induced nauesa and vomiting – a real life study. San Antonio Breast Cancer Symposium 2019; 2019: P2-12-02
• 37 Aapro M, Schwartzberg L. Efficacy of intravenous (IV) NEPA and oral NEPA, fixed NK1/5-HT3 receptor antagonist combination agents, for prevention of chemotherapy-induced nausea and vomiting (CINV) following anthracycline-cyclophosphamide (AC)-based chemotherapy. San Antonio Breast Cancer Symposium 2019; P2-12-04
• 38 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7-30