Update Mammakarzinom 2020 Teil 4 – fortgeschrittenes Mammakarzinom

Zusammenfassung

Nachdem in den letzten Jahren bei der Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom zunehmend Substanzen mit einer guten Effektivität zum Einsatz kommen, welche spezifische Signalwege angreifen, sind nun neue Therapien und Ansätze hinzugekommen, die sich tatsächlich auf ganz spezifische Veränderungen beziehen wie die Behandlung von Patientinnen mit HR+/HER2− Tumoren mit einer PIK3CA-Mutation. Ebenso ist die Behandlung von Patientinnen mit einer BRCA1- oder BRCA2-Mutation durch die Einführung der PARP-Inhibitoren verbessert worden. Nun wird zunehmend versucht, Therapieindikationen aufgrund molekularer Muster auszudehnen und weitere Patientinnen zu identifizieren, die von einer Therapie profitieren könnten, und die neu etablierten Therapiemethoden in bestehende Therapiesequenzen einzubinden. Diese Übersichtsarbeit fasst die neuesten Erkenntnisse in diesem Zusammenhang zusammen.

Schlüsselwörter

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

Publication History

Received: 30 July 2020

Accepted after revision: 23 September 2020

Article published online:
06 November 2020

• References/Literatur

• 1 Schutz F, Fasching PA, Welslau M. et al. Update Breast Cancer 2019 Part 4 – Diagnostic and Therapeutic Challenges of New, Personalised Therapies for Patients with Early Breast Cancer. Geburtshilfe Frauenheilkd 2019; 79: 1079-1089
• 2 Welslau M, Hartkopf AD, Muller V. et al. Update Breast Cancer 2019 Part 5 – Diagnostic and Therapeutic Challenges of New, Personalised Therapies in Patients with Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2019; 79: 1090-1099
• 3 Hartkopf AD, Muller V, Wockel A. et al. Update Breast Cancer 2019 Part 1 – Implementation of Study Results of Novel Study Designs in Clinical Practice in Patients with Early Breast Cancer. Geburtshilfe Frauenheilkd 2019; 79: 256-267
• 4 Janni W, Schneeweiss A, Muller V. et al. Update Breast Cancer 2019 Part 2 – Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice. Geburtshilfe Frauenheilkd 2019; 79: 268-280
• 5 Lux MP, Nabieva N, Hartkopf AD. et al. Therapy Landscape in Patients with Metastatic HER2-Positive Breast Cancer: Data from the PRAEGNANT Real-World Breast Cancer Registry. Cancers (Basel) 2019; 11: 10
• 6 Murthy RK, Loi S, Okines A. et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2020; 382: 597-609
• 7 Lin NU, Borges V, Anders C. 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;
• 8 Rugo HS, Im SA, Wright GLS. et al. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). J Clin Oncol 2019; 37: 1000-1000
• 9 Ma F, Ouyang Q, Li W. et al. Pyrotinib or Lapatinib Combined With Capecitabine in HER2-Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study. J Clin Oncol 2019; 37: 2610-2619
• 10 Xu B, Yan M, Ma F. et al. Pyrotinib or lapatinib plus capecitabine for HER2+ metastatic breast cancer (PHOEBE): A randomized phase III trial. J Clin Oncol 2020; 38: 1003-1003
• 11 Modi S, Saura C, Yamashita T. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med 2019;
• 12 Hartkopf AD, Muller V, Wockel A. et al. Translational Highlights in Breast and Ovarian Cancer 2019 – Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy. Geburtshilfe Frauenheilkd 2019; 79: 1309-1319
• 13 Shurin MR, Naiditch H, Gutkin DW. et al. ChemoImmunoModulation: immune regulation by the antineoplastic chemotherapeutic agents. Curr Med Chem 2012; 19: 1792-1803
• 14 Fermaintt CS, Mooberry SL, Risinger AL. Eribulin promotes a distinct immunogenic gene expression signature as compared with paclitaxel. AACR Annual Meeting 2020; Abstr. 4896.
• 15 Tolaney SM, Kalinsky K, Kaklamani VG. et al. A phase Ib/II study of eribulin (ERI) plus pembrolizumab (PEMBRO) in metastatic triple-negative breast cancer (mTNBC) (ENHANCE 1). J Clin Oncol 2020; 38: 1015-1015
• 16 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
• 17 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
• 18 Fasching PA, Hu C, Hart SN. et al. Cancer predisposition genes in metastatic breast cancer – Association with metastatic pattern, prognosis, patient and tumor characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX. Philadelphia (PA): AACR Cancer Res 2018; 78: Abstr. PD1-02
• 19 Couch FJ, Hart SN, Sharma P. et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 2015; 33: 304-311
• 20 Fasching PA, Loibl S, Hu C. et al. BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study. J Clin Oncol 2018; 36: 2281-2287
• 21 Pohl-Rescigno E, Hauke J, Loibl S. et al. Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer: A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol 2020;
• 22 Hahnen E, Lederer B, Hauke J. et al. Germline Mutation Status, Pathological Complete Response, and Disease-Free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial. JAMA Oncol 2017; 3: 1378-1385
• 23 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
• 24 Tung NM, Robson ME, Ventz S. et al. TBCRC048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). J Clin Oncol 2020; 38: 1002-1002
• 25 Hartkopf AD, Huober J, Volz B. et al. Treatment landscape of advanced breast cancer patients with hormone receptor positive HER2 negative tumors – Data from the German PRAEGNANT breast cancer registry. Breast 2018; 37: 42-51
• 26 Hartkopf AD, Emons J, Lux MP. et al. Clinical endpoints in real-world registry studies PRAEGNANT network for women with advanced breast cancer. Onkologe 2020; 26: 530-541
• 27 Fasching PA, Brucker SY, Fehm TN. et al. Biomarkers in Patients with Metastatic Breast Cancer and the PRAEGNANT Study Network. Geburtshilfe Frauenheilkd 2015; 75: 41-50
• 28 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
• 29 Slamon DJ, Neven P, Chia S. et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med 2019;
• 30 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;
• 31 Turner NC, Ro J, Andre F. et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209-219
• 32 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
• 33 Im SA, Lu YS, Bardia A. et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019;
• 34 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
• 35 Finn RS, Crown JP, Lang I. et al. 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
• 36 Finn RS, Martin M, Rugo HS. et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375: 1925-1936
• 37 Turner NC, Slamon DJ, Ro J. et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med 2018; 379: 1926-1936
• 38 Llombart-Cussac A, Pérez-García JM, Bellet M. et al. PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with estrogen receptor (ER)[+]/HER2[−] metastatic breast cancer. J Clin Oncol 2020; 38: 1007-1007
• 39 Rugo HS, Lerebours F, Ciruelos E. et al. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with PIK3CA-mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results. J Clin Oncol 2020; 38: 1006-1006
• 40 Cortes J, Lipatov O, Im SA. et al. KEYNOTE-119: Phase 3 Study of Pembrolizumab versus Single-Agent Chemotherapy for Metastatic Triple-Negative Breast Cancer (mTNBC). Ann Oncol 2019; 30 (Suppl. 05) v851-v934 doi:10.1093/annonc/mdz1394
• 41 Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. N Engl J Med 2017; 377: 2500-2501
• 42 Hellmann MD, Ciuleanu TE, Pluzanski A. et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 378: 2093-2104
• 43 Waqar SN, Govindan R. The Mystic Role of Tumor Mutational Burden in Selecting Patients With Lung Cancer for First-Line Immunotherapy. JAMA Oncol 2020;
• 44 Chumsri S, Sokol ES, Soyano-Muller AE. et al. Durable Complete Response With Immune Checkpoint Inhibitor in Breast Cancer With High Tumor Mutational Burden and APOBEC Signature. J Natl Compr Canc Netw 2020; 18: 517-521
• 45 Cortes J, Cescon DW, Rugo HS. et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. J Clin Oncol 2020; 38: 1000-1000
• 46 Sharma P, Rodler E, Barlow WE. et al. Results of a phase II randomized trial of cisplatin +/− veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416). J Clin Oncol 2020; 38: 1001-1001