Update Mammakarzinom 2020 Teil 4 – fortgeschrittenes Mammakarzinom

Hans Tesch; Volkmar Müller; Achim Wöckel; Johannes Ettl; Erik Belleville; Florian Schütz; Andreas Hartkopf; Marc Thill; Jens Huober; Peter A. Fasching; Hans-Christian Kolberg; Carla E. Schulmeyer; Manfred Welslau; Friedrich Overkamp; Tanja N. Fehm; Michael P. Lux; Andreas Schneeweiss; Diana Lüftner; Wolfgang Janni

doi:10.1055/a-1331-8621

Senologie - Zeitschrift für Mammadiagnostik und -therapie, Table of Contents

CC BY-NC-ND 4.0 · Senologie - Zeitschrift für Mammadiagnostik und -therapie 2021; 18(01): 49-57
DOI: 10.1055/a-1331-8621

Wissenschaftliche Arbeit

Update Mammakarzinom 2020 Teil 4 – fortgeschrittenes Mammakarzinom

Update Breast Cancer 2020 Part 4 – Advanced Breast Cancer

Hans Tesch

¹Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt

,

Volkmar Müller

²Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg

,

Achim Wöckel

³Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg

,

Johannes Ettl

⁴Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich

,

Erik Belleville

⁵ClinSol GmbH & Co. KG, Würzburg

,

Florian Schütz

⁶Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg

,

Andreas Hartkopf

⁷Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Marc Thill

⁸Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt

,

Jens Huober

⁹Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm

,

Peter A. Fasching

¹⁰Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen

,

Hans-Christian Kolberg

¹¹Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop

,

Carla E. Schulmeyer

¹⁰Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen

,

Manfred Welslau

¹²Onkologie Aschaffenburg, Aschaffenburg

,

Friedrich Overkamp

¹³OncoConsult Overkamp, Berlin

,

Tanja N. Fehm

¹⁴Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf

,

Michael P. Lux

¹⁵Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten

,

Andreas Schneeweiss

¹⁶National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg

,

Diana Lüftner

¹⁷Charité University Hospital, Department of Hematology, Oncology and Tumour Immunology, Berlin

,

Wolfgang Janni

⁹Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm

› Author Affiliations

Abstract

Zusammenfassung

Nachdem in den letzten Jahren bei der Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom zunehmend Substanzen mit einer guten Effektivität zum Einsatz kommen, die 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.

Abstract

Substances with good effectiveness that intervene in specific signalling pathways have been used increasingly in recent years in the treatment of patients with advanced breast cancer, and new therapies and approaches have now been added, which actually relate to quite specific changes, such as the treatment of patients with HR+/HER2 tumours with a PIK3CA mutation. The treatment of patients with a BRCA1 or BRCA2 mutation has also been improved by the introduction of PARP inhibitors. Attempts are now being made increasingly to extend treatment indications based on molecular patterns, to identify other patients who could benefit from a treatment and to integrate the newly established treatment methods in existing therapy sequences. This review articles summarises the latest information in this connection.

Schlüsselwörter

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

Key words

advanced breast cancer - metastases - treatment - mutation testing - immunotherapy - PARP - CDK4/6 - BRCA1/2 - PD‑L1

Full Text

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 SA, 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 Gepar-Quinto 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:810.1093/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 jr 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 firstline 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:810.1093/annonc/mdz1394
41 Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD1 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