Update Breast Cancer 2022 Part 6 – Advanced-Stage Breast Cancer

Diana Lüftner; Michael P. Lux; Tanja N. Fehm; Manfred Welslau; Volkmar Müller; Florian Schütz; Peter A. Fasching; Wolfgang Janni; Christoph Thomssen; Isabell Witzel; Milena Beierlein; Erik Belleville; Michael Untch; Marc Thill; Nina Ditsch; Bahriye Aktas; Maggie Banys-Paluchowski; Cornelia Kolberg-Liedtke; Achim Wöckel; Hans-Christian Kolberg; Nadia Harbeck; Elmar Stickeler; Hans Tesch; Andreas D. Hartkopf

doi:10.1055/a-2018-9184

Geburtshilfe und Frauenheilkunde, Table of Contents

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2023; 83(03): 299-309
DOI: 10.1055/a-2018-9184

GebFra Science

Review

Update Mammakarzinom 2022 Teil 6 – Brustkrebs in fortgeschrittenen Krankheitsstadien

Article in several languages: English | deutsch

Diana Lüftner

¹Immanuel Hospital Märkische Schweiz, Buckow; Medical University of Brandenburg Theodor-Fontane, Brandenburg, Germany

,

Michael P. Lux

²Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, St. Vincenz Krankenhaus GmbH, Paderborn, Germany

,

Tanja N. Fehm

³Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany

,

Manfred Welslau

⁴Onkologie Aschaffenburg, Aschaffenburg, Germany

,

Volkmar Müller

⁵Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany

,

Florian Schütz

⁶Gynäkologie und Geburtshilfe, Diakonissen-Stiftungs-Krankenhaus Speyer, Speyer, Germany

,

Peter A. Fasching

⁷Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Wolfgang Janni

⁸Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Christoph Thomssen

⁹Department of Gynaecology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

,

Isabell Witzel

⁵Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany

,

Milena Beierlein

⁷Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Erik Belleville

¹⁰ClinSol GmbH & Co. KG, Würzburg, Germany

,

Michael Untch

¹¹Clinic for Gynecology and Obstetrics, Breast Cancer Center, Gynecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin, Germany

,

Marc Thill

¹²Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt, Germany

,

Nina Ditsch

¹³Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany

,

Bahriye Aktas

¹⁴Department of Gynecology, University of Leipzig Medical Center, Leipzig, Germany

,

Maggie Banys-Paluchowski

¹⁵Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

,

Cornelia Kolberg-Liedtke

¹⁶Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany

,

Achim Wöckel

¹⁷Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany

,

Hans-Christian Kolberg

¹⁸Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany

,

Nadia Harbeck

¹⁹Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich, Germany

,

Elmar Stickeler

²⁰Department of Obstetrics and Gynecology, Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf), University Hospital of RWTH Aachen, Aachen, Germany

,

Hans Tesch

²¹Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany

,

Andreas D. Hartkopf

⁸Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

› Author Affiliations

Abstract

Zusammenfassung

Die in den letzten Jahren begonnenen großen Studienprogramme zu den CDK4/6-Inhibitoren, den zielgerichteten Therapien und den Antikörper-Medikament-Konjugaten resultieren in Ergebnisse, die von aktuellen Studien auf internationalen Kongressen und Fachzeitschriften veröffentlicht werden. In diesem Zusammenhang sind neue Ergebnisse der großen CDK4/6-Inhibitor-Studien verfügbar. Auch werden zunehmend Daten von großen genomischen Studien zu Effektivitäts- und Resistenzmechanismen für Patientinnen, die mit CDK4/6-Inhibitoren behandelt worden sind, veröffentlicht. Basierend auf diesen Ergebnissen sollten nicht zuletzt Studien in Bezug auf Kombinationspartner und Therapiesequenzen geplant werden. Mit Sacituzumab Govitecan ist aufgrund neuester Veröffentlichungen nun ein zweites Antikörper-Medikament-Konjugat vorhanden, das bei hormonrezeptorpositiven (HRpos)/HER2-negativen (HER2neg) Patientinnen einen Gesamtüberlebensvorteil mit sich bringt. Diese Übersichtsarbeit fasst die neuesten Entwicklungen zusammen und ordnet sie in den aktuellen Forschungsstand ein.

Schlüsselwörter

fortgeschrittener Brustkrebs - Chemotherapie - Therapiestandard

Full Text

References

References/Literatur
1 Slamon DJ, Neven P, Chia S. et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol 2021; 32: 1015-1024
2 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
3 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; 36: 2465-2472
4 Sledge jr. GW, Toi M, Neven P. et al. MONARCH 2: 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
5 Turner NC, OʼLeary B, Cutts R. et al. Genetic landscape of resistance to CDK4/6 inhibition in circulating tumor DNA (ctDNA) analysis of the PALOMA3 trial of palbociclib and fulvestrant versus placebo and fulvestrant. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 1001
6 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;
7 Cristofanilli M, Turner NC, Bondarenko I. et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016; 17: 425-439
8 Tripathy D, Im SA, 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;
9 Finn RS, Martin M, Rugo HS. et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375: 1925-1936
10 Hortobagyi GN, Stemmer SM, Burris HA. et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med 2022; 386: 942-950
11 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
12 Im SA, Lu YS, Bardia A. et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019; 381: 307-316
13 Slamon DJ, Neven P, Chia S. et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med 2020; 382: 514-524
14 Turner NC, Ro J, Andre F. et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209-219
15 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
16 Luftner D, Schutz F, Stickeler E. et al. Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2022; 82: 215-225
17 Goetz MP, Toi M, Huober J. et al. MONARCH 3: Interim overall survival (OS) results of abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+, HER2- advanced breast cancer (ABC). Ann Oncol 2022; 33 (Suppl. 07) S808-S869
18 European Medicines Agency. Verzenios. 2022. Accessed November 20, 2022 at: https://www.emaeuropa.eu/en/medicines/human/summaries-opinion/verzenios
19 Allison KH, Hammond MEH, Dowsett M. et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol 2020; 38: 1346-1366
20 Wang J, Li Q, Yuan J. et al. CDK4/6 inhibitor-SHR6390 exerts potent antitumor activity in esophageal squamous cell carcinoma by inhibiting phosphorylated Rb and inducing G1 cell cycle arrest. J Transl Med 2017; 15: 127
21 Long F, He Y, Fu H. et al. Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models. Cancer Sci 2019; 110: 1420-1430
22 Xu B, Zhang Q, Zhang P. et al. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med 2021; 27: 1904-1909
23 Xu B, Zhang QY, Zhang P. et al. Dalpiciclib plus letrozole or anastrozole as first-line treatment for HR+/HER2- advanced breast cancer (DAWNA-2): A phase III trial. Ann Oncol 2022; 33 (Suppl. 07) S808-S869
24 Bidard FC, Hardy-Bessard AC, Dalenc F. et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2022; 23: 1367-1377
25 Laine M, Fanning SW, Chang YF. et al. Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer. Breast Cancer Res 2021; 23: 54
26 Andreano KJ, Baker JG, Park S. et al. The Dysregulated Pharmacology of Clinically Relevant ESR1 Mutants is Normalized by Ligand-activated WT Receptor. Mol Cancer Ther 2020; 19: 1395-1405
27 Goetz MP, Plourde P, Stover DG. et al. Open-label, randomized study of lasofoxifene (LAS) vs. fulvestrant (Fulv) for women with locally advanced/metastatic ER+/HER2- breast cancer (mBC), an estrogen receptor 1 (ESR1) mutation, and disease progression on aromatase (AI) and cyclin-dependent kinase 4/6 (CDK4/6i) inhibitors. Ann Oncol 2022; 33 (Suppl. 07) S808-S869
28 Safonov A, Bandlamudi C, Tallón de Lara P. et al. Comprehensive genomic profiling of patients with breast cancer identifies germline-somatic interactions mediating therapy resistanc. San Antonio Breast Cancer Symposium 2021; 2021: GS4-08
29 Marra A, Gazzo A, Gupta A. et al. Mutational signature analysis reveals patterns of genomic instability linked to resistance to endocrine therapy (ET) ± CDK 4/6 inhibition (CDK4/6i) in estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC). Ann Oncol 2022; 33 (Suppl. 07) S88-S121
30 Alexandrov LB, Stratton MR. Mutational signatures: the patterns of somatic mutations hidden in cancer genomes. Curr Opin Genet Dev 2014; 24: 52-60
31 Alexandrov LB, Kim J, Haradhvala NJ. et al. The repertoire of mutational signatures in human cancer. Nature 2020; 578: 94-101
32 COSMIC. Mutational Signatures (v3.3 – June 2022)- Single Base Substitution (SBS) Signatures. 2022. Accessed November 12, 2022 at: https://cancer.sanger.ac.uk/signatures/sbs/
33 clinicaltrials.gov. Comprehensive Analysis of Spatial, Temporal and Molecular Patters of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients (CAPTOR-BC). 2022. Accessed July, 16, 2022 at: https://clinicaltrials.gov/ct2/show/NCT05452213
34 clinicaltrials.gov. Combination of Abemaciclib and Endocrine Therapy in Hormone Receptor Positive HER2 Negative Locally Advanced or Metastatic Breast Cancer With Focus on Digital Side Effect Management (MINERVA). 2022. Accessed June 26, 2022 at: https://clinicaltrials.gov/ct2/show/NCT05362760
35 Bidard FC, Kaklamani VG, Neven P. et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol 2022; 40: 3246-3256
36 AstraZeneca. Camizestrant significantly improved progression-free survival vs. Faslodex in SERENA-2 Phase II trial in advanced ER-positive breast cancer. 2022. Accessed November 20, 2022 at: https://www.astrazeneca.com/media-centre/press-releases/2022/camizestrant-significantly-improved-progression-free-survival.html
37 Tolaney SM, Chan A, Petrakova K. et al. AMEERA-3, a phase II study of amcenestrant (AMC) versus endocrine treatment of physicianʼs choice (TPC) in patients (pts) with endocrine-resistant ER+/HER2− advanced breast cancer (aBC). Ann Oncol 2022; 33 (Suppl. 07) S80-S121
38 Jimenez MM, Lim E, Gregor MCM. et al. Giredestrant (GDC-9545) vs. physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase II, randomised, open-label acelERA BC study. Ann Oncol 2022; 33 (Suppl. 07) S808-S869
39 Sanofi. Sanofi provides update on amcenestrant clinical development program. 2022. Accessed November 03, 2022 at: https://www.sanofi.com/en/media-room/press-releases/2022/2022-08-17-05-30-00-2499668
40 Di Cosimo S, Perez-Garcia JM, Bellet M. et al. Palbociclib with Fulvestrant or Letrozole in Endocrine-Sensitive Patients with HR-Positive/HER2-Negative Advanced Breast Cancer: A Detailed Safety Analysis of the Randomized PARSIFAL Trial. Oncologist 2023; 28: 23-32
41 Ruiz-Borrego M, Guerrero-Zotano A, Bermejo B. et al. Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study. Breast Cancer Res Treat 2019; 177: 115-125
42 Rugo HS, Bardia A, Marmé F. et al. Primary results from TROPiCS-02: A randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physicianʼs choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. J Clin Oncol 2022; 40: LBA1001-LBA1001
43 Rugo HS, Bardia A, Marmé F. et al. Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs. treatment of physicianʼs choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). Ann Oncol 2022; 33 (Suppl. 07) S808-S869
44 Engler T, Fasching PA, Luftner D. et al. Implementation of CDK4/6 Inhibitors and its Influence on the Treatment Landscape of Advanced Breast Cancer Patients – Data from the Real-World Registry PRAEGNANT. Geburtshilfe Frauenheilkd 2022; 82: 1055-1067
45 Hartkopf A. Therapy landscapes and molecular markers, the German PRAEGNANT registry. ESMO Breast Cancer Conference 2022. 2022. Accessed November 10, 2022 at: https://oncologypro.esmo.org/meeting-resources/esmo-breast-cancer-congress/therapy-landscapes-and-molecular-markers-the-german-praegnant-registry
46 Modi S, Jacot W, Yamashita T. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med 2022; 387: 9-20
47 Rugo HS, Bardia A, Marme F. et al. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. J Clin Oncol 2022; 40: 3365-3376
48 Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res 2015; 3: 436-443
49 Opzoomer JW, Sosnowska D, Anstee JE. et al. Cytotoxic Chemotherapy as an Immune Stimulus: A Molecular Perspective on Turning Up the Immunological Heat on Cancer. Front Immunol 2019; 10: 1654
50 Munzone E, Regan MM, Cinieri S. et al. A randomized phase II trial of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) vs. weekly paclitaxel (P) as first- or second-line treatment in patients (pts) with ER+/HER2- metastatic breast cancer (MBC): The METEORA-II trial (IBCSG 54-16). Ann Oncol 2022; 33 (Suppl. 07) S88-S121
51 clinicaltrials.gov. NCT05033769. Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer (AIRE). NIH US National Library of Medicine 2022; Accessed November 01, 2022 at: https://clinicaltrials.gov/ct2/show/NCT05033769
52 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
53 OʼBrien NA, McDonald K, Tong L. et al. Targeting PI3K/mTOR overcomes resistance to HER2-targeted therapy independent of feedback activation of AKT. Clin Cancer Res 2014; 20: 3507-3520
54 Loibl S, von Minckwitz G, Schneeweiss A. et al. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol 2014; 32: 3212-3220
55 Schlam I, Tarantino P, Tolaney SM. Overcoming Resistance to HER2-Directed Therapies in Breast Cancer. Cancers (Basel) 2022; 14: 3996
56 Xu B, Yan M, Ma F. et al. Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer (PHILA): A randomized phase III trial. Ann Oncol 2022; 33 (Suppl. 07) S808-S869
57 Swain SM, Baselga J, Kim SB. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372: 724-734
58 Baselga J, Cortes J, Kim SB. et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012; 366: 109-119
59 Muller V, Welslau M, Luftner D. et al. Update Breast Cancer 2022 Part 2 – Advanced Stage Breast Cancer. Geburtshilfe Frauenheilkd 2022; 82: 590-600
60 Aktas B, Fehm TN, Welslau M. et al. Update Breast Cancer 2022 Part 4 – Advanced-Stage Breast Cancer. Geburtshilfe Frauenheilkd 2022; 82: 922-931
61 Ditsch N, Stickeler E, Behrens A. et al. Update Breast Cancer 2021 Part 2 – Advanced Stages, Long-Term Consequences and Biomarkers. Geburtshilfe Frauenheilkd 2021; 81: 539-548
62 Tesch H, Muller V, Wockel A. et al. Update Breast Cancer 2020 Part 4 – Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2020; 80: 1115-1122
63 André F, Nadal JC, Denys H. et al. Final overall survival (OS) for abemaciclib plus trastuzumab ± fulvestrant versus trastuzumab plus chemotherapy in patients with HR+, HER2+ advanced breast cancer (monarcHER): A randomized, open-label, phase II trial. Ann Oncol 2022; 33 (Suppl. 07) S808-S869