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DOI: 10.1055/a-1816-1687
Update Mammakarzinom 2021 Teil 5 – fortgeschrittenes Mammakarzinom
Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer![](https://www.thieme-connect.de/media/senologie/202202/lookinside/thumbnails/seno-18161687_10-1055-a-1816-1687-1.jpg)
Zusammenfassung
Trotz der COVID-19-Pandemie und weitgehend virtueller Kongresse schreitet die Innovation in Bezug auf die Behandlung von Patientinnen mit Mammakarzinom mit ungebremster Geschwindigkeit fort. Dieser Übersichtsartikel fasst die aktuellen Entwicklungen zusammen. Die ersten Daten zum Gesamtüberleben für eine Therapie mit einem CDK4/6-Inhibitor in Kombination mit einem Aromatasehemmer bei nicht vorbehandelten, postmenopausalen Patientinnen in der ersten fortgeschrittenen Therapielinie wurden veröffentlicht. Ebenso zeigte eine Studie, die Trastuzumab-Deruxtecan mit Trastuzumab-Emtansin verglich, einen deutlichen Vorteil in Bezug auf das progressionsfreie Überleben. Die Kenntnisse über Biomarker, die eine Therapie mit einem Checkpoint-Inhibitor besonders effektiv machen, nehmen zu, und neue Substanzen wie die oralen selektiven Östrogenrezeptor-Destabilisatoren (SERDs) halten Einzug in die klinische Entwicklung und schließen die ersten Phase-III-Studien ab.
Abstract
Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumabemtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials.
Schlüsselwörter
BRCA (breast cancer associated gene) - Genetik - Her‑2/neu (humaner epidermaler Wachstumsfaktor‑Rezeptor) - Hormonrezeptor - Mammakarzinom - Brust - MammaKey words
BRCA (breast cancer associated gene) - genetics - Her‑2/neu (human epidermal growth factor receptor) - hormonal receptor - breast cancer - breastPublikationsverlauf
Eingereicht: 06. Dezember 2021
Angenommen: 18. Dezember 2021
Artikel online veröffentlicht:
10. Juni 2022
© 2022. This article was originally published by Thieme as Diana Lüftner et al., Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer. Geburtsh Frauenheilk 2022; 82: 215–225 as an open access article under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. https://creativecommons.org/licenses/by-nc-nd/4.0/
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Literatur
- 1 Jordan VC. Third annual William L. McGuire Memorial Lecture. “Studies on the estrogen receptor in breast cancer” – 20 years as a target for the treatment and prevention of cancer. Breast Cancer Res Treat 1995; 36: 267-285
- 2 Drugs.com. Herceptin FDA Approval History. Online (Stand: 14.11.2021): https://www.drugs.com/history/herceptin.html#
- 3 Hortobagyi GN, Stemmer SM, Burris III HA. et al. LBA17_PR – Overall survival (OS) results from the phase III MONALEESA‑2 (ML‑2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol 2021; 32 (Suppl. 05) S1283-S1346
- 4 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
- 5 Tripathy D, Im SA, Colleoni M. et al. Abstract PD2-04: Updated overall survival (OS) results from the phase III MONALEESA‑7 trial of pre- or perimenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Cancer Res 2021; 81 (04) PD2-04
- 6 Cristofanilli M, Rugo HS, Im SA. et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA‑3. J Clin Oncol 2021; 39 (15) 1000
- 7 Harbeck N, Rastogi P, Martin M. et al. Adjuvant Abemaciclib Combined With Endocrine Therapy for High-Risk Early Breast Cancer: Updated Efficacy and Ki-67 Analysis From the monarchE Study. Ann Oncol 2021; 32: 1571-1581
- 8 OʼLeary B, Cutts RJ, Huang X. et al. Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer. J Natl Cancer Inst 2021; 113: 309-317
- 9 Andre F, Su F, Solovieff N. et al. Pooled ctDNA analysis of the MONALEESA (ML) phase III advanced breast cancer (ABC) trials. J Clin Oncol 2020; 38 (15) 1009
- 10 Bidard FC, Callens C, Dalenc F. et al. Prognostic impact of ESR1 mutations in ER+HER2-MBC patients prior treated with first line AI and palbociclib: An exploratory analysis of the PADA‑1 trial. J Clin Oncol 2020; 38 (15) 1010
- 11 European Medicines Agency. Summary of opinion (post authorisation): Faslodex (fulvestrant). Online (Stand: 16.10.2021): https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summarypositive-opinion-faslodex_en-0.pdf
- 12 Ruíz-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
- 13 Robertson JF. Fulvestrant (Faslodex) – how to make a good drug better. Oncologist 2007; 12: 774-784
- 14 Menari Group, Radius Health. Menarini Group and Radius Health Announce Positive Phase 3 Topline Results from the EMERALD Trial Evaluating Elacestrant in Breast Cancer. Online (Stand: 22.10.2021): https://ir.radiuspharm.com/news-releases/news-release-details/menarini-groupand-radius-health-announce-positive-phase-3
- 15 Snyder LB, Flanagan JJ, Qian Y. et al. Abstract 44: The discovery of ARV‑471, an orally bioavailable estrogen receptor degrading PROTAC for the treatment of patients with breast cancer. Cancer Res 2021; 81 (13) 44
- 16 ClinicalTrials.gov. Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA‑6) (SERENA‑6). Online (Stand: 24.10.2021): https://clinicaltrials.gov/ct2/show/NCT04964934
- 17 André 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
- 18 ClinicalTrials.gov. Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-postitive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor. (EPIK‑B5). Online (Stand: 24.10.2021): https://clinicaltrials.gov/ct2/show/NCT05038735
- 19 Lux MP, Schneeweiss A, Hartkopf AD. et al. Update Breast Cancer 2020 Part 5 – Moving Therapies From Advanced to Early Breast Cancer Patients. Geburtshilfe Frauenheilkd 2021; 81: 469-480
- 20 SOLTI Study Group. SOLTI launches HARMONIA, an international phase III study to identify the best therapeutic option for selected patients with aggressive HR+/HER2- advanced breast cancer. Online (Stand: 24.10.2021): https://www.gruposolti.org/ndp-harmonia-2021/?lang=en
- 21 Katzorke N, Rack BK, Haeberle L. et al. Prognostic value of HER2 on breast cancer survival. J Clin Oncol 2013; 31 (15) 640
- 22 Taran FA, Fasching PA, Volz B. et al. Abstract P5-21-09: Overall survival of metastatic breast cancer patients – data from the PRAEGNANT breast cancer registry. Cancer Res 2018; 78: P5-21-09
- 23 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
- 24 Cortés J, Kim S, Chung W. et al. LBA1 – Trastuzumab deruxtecan (T‑DXd) vs. trastuzumab emtansine (T‑DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study. Ann Oncol 2021; 32 (Suppl. 05) S1283-S1346
- 25 Michel LL, Hartkopf AD, Fasching PA. et al. Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T‑DM1) after Previous Treatment with Pertuzumab. Cancers (Basel) 2020; 12: 3021
- 26 Modi S, Saura C, Yamashita T. et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med 2020; 382: 610-621
- 27 European Medicines Agency. Enhertu – Annex I. Summary of Product Characteristics. Online (Stand: 24.10.2021): https://www.ema.europa.eu/en/documents/product-information/enhertu-epar-productinformation_en.pdf
- 28 Saura Manich C, OʼShaughnessy J, Aftimos PF. et al. LBA15 – Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physicianʼs choice treatment in patients with pretreated HER2-positive locally advanced or metastatic breast cancer. Ann Oncol 2021; 32 (Suppl. 05) S1283-S1346
- 29 Hanka LJ, Dietz A, Gerpheide SA. et al. CC-1065 (NSC-298223), a new antitumor antibiotic. Production, in vitro biological activity, microbiological assays and taxonomy of the producing microorganism. J Antibiot (Tokyo) 1978; 31: 1211-1217
- 30 Yuan Z, Huang JJ, Hua X. et al. Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for metastatic breast cancer with hormone receptor-positive and HER2-positive: The sysucc-002 randomized clinical trial. J Clin Oncol 2021; 39 (15) 1003
- 31 Rugo HS, Schmid P, Cescon DW. et al. Abstract GS3-01: Additional efficacy endpoints from the phase 3 KEYNOTE‑355 study of pembrolizumab plus chemotherapy vs. placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium, San Antonio, TX, USA. December 8-11 2020; DOI: 10.1158/1538-7445.SABCS20-GS3-01.
- 32 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
- 33 Miles D, Gligorov J, André F. et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol 2021; 32: 994-1004
- 34 Denkert C, von Minckwitz G, Darb-Esfahani S. et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 2018; 19: 40-50
- 35 Würfel F, Erber R, Huebner H. et al. TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients – First Results on the Influence of Tumor-Infiltrating Lymphocytes. Breast Care (Basel) 2018; 13: 8-14
- 36 Fasching PA, Denkert C, Benz S. et al. Abstract PD5-08: Tumor immunecell activity assessed by RNAseq is an independent predictor of therapy response and prognosis after neoadjuvant chemotherapy in HER2 negative breast cancer patients – An analysis of the GeparSepto trial. Proceedings of the 2019 San Antonio Breast Cancer Symposium, San Antonio, TX, USA. December 10-14 2019; DOI: 10.1158/1538-7445. SABCS19-PD5-08.
- 37 Sinn BV, Loibl S, Hanusch CA. et al. Immune-related Gene Expression Predicts Response to Neoadjuvant Chemotherapy but not Additional Benefit from PD‑L1 Inhibition in Women with Early Triple-negative Breast Cancer. Clin Cancer Res 2021; 27: 2584-2591
- 38 Emens LA, Goldstein LD, Schmid P. et al. The tumor microenvironment (TME) and atezolizumab + nab-paclitaxel (A+nP) activity in metastatic triple-negative breast cancer (mTNBC): IMpassion130. J Clin Oncol 2021; 39 (15) 1006
- 39 Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature 2017; 541: 321-330
- 40 Burstein MD, Tsimelzon A, Poage GM. et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 2015; 21: 1688-1698
- 41 Cortes J, Cescon DW, Rugo HS. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 2020; 396: 1817-1828
- 42 Rugo HS, Cortés J, Cescon DW. et al. LBA16 – KEYNOTE‑355: Final results from a randomized, double-blind phase III study of first-line pembrolizumab + chemotherapy vs. placebo + chemotherapy for metastatic TNBC. Ann Oncol 2021; 32 (Suppl. 05) S1283-S1346
- 43 Turner NC, Ro J, André F. et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209-219
- 44 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
- 45 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
- 46 Finn RS, Martin M, Rugo HS. et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375: 1925-1936
- 47 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
- 48 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; 19: 904-915
- 49 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
- 50 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
- 51 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 2020; 6: 116-124
- 52 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
- 53 Jhaveri K, Juric D, Yap YS. et al. A Phase I Study of LSZ102, an Oral Selective Estrogen Receptor Degrader, with or without Ribociclib or Alpelisib, in Patients with Estrogen Receptor-Positive Breast Cancer. Clin Cancer Res 2021; 27: 5760-5770
- 54 Maglakelidze M, Bulat I, Ryspayeva D. et al. Rintodestrant (G1 T48), an oral selective estrogen receptor degrader, in combination with palbociclib for ER+/HER2– advanced breast cancer: Phase 1 results. J Clin Oncol 2021; 39 (15) 1063
- 55 Aftimos P, Neven P, Pegram M. et al. Abstract PS12-04: Rintodestrant (G1 T48), an oral selective estrogen receptor degrader in ER+/HER2- locally advanced or metastatic breast cancer: Updated phase 1 results and dose selection. Cancer Res 2021; 81 (04) PS12-04
- 56 Bardia A, Kaklamani V, Wilks S. et al. Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer. J Clin Oncol 2021; 39: 1360-1370
- 57 Hurvitz SA, Park YH, Bardia A. et al. LBA14 – Neoadjuvant giredestrant (GDC-9545) + palbociclib (palbo) vs. anastrozole (A) + palbo in postmenopausal women with oestrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+/HER2– eBC): Interim analysis of the randomised, open-label, phase II coopERA BC study. Ann Oncol 2021; 32 (Suppl. 05) S1283-S1346 DOI: 10.1016/j.annonc.2021.08.2086.
- 58 Liang J, Zbieg JR, Blake RA. et al. GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer. J Med Chem 2021; 64: 11841-11856
- 59 Metcalfe C, Ingalla E, Blake RA. et al. Abstract P5-04-07: GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes. Cancer Res 2019; 79 (04) P5-04-07
- 60 Chandarlapaty S, Linden HM, Neven P. et al. 264P – AMEERA‑1: Subgroup analyses of phase I/II study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with palbociclib in postmenopausal women with ER+/human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (aBC). Ann Oncol 2021; 32 (Suppl. 05) S457-S515
- 61 Chandarlapaty S, Linden HM, Neven P. et al. AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with palbociclib (palbo) in postmenopausal women with ER+/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). J Clin Oncol 2021; 39 (Suppl. 15) 1058-1058 DOI: 10.1200/JCO.2021.39.15_suppl.1058.
- 62 Shomali M, Sun F, Besret L. et al. Abstract 739: Preclinical and clinical activity of SAR439859, Amcenestrant, a next generation SERD. Cancer Res 2021; 81: 739 DOI: 10.1158/1538-7445.AM2021-739.
- 63 Scott JS, Moss TA, Stokes S. et al. Abstract 5674: Discovery of AZD9833, an oral small molecule selective degrader of the estrogen receptor (SERD). Cancer Res 2020; 80 (16) 5674
- 64 Bhagwat SV, Zhao B, Shen W. et al. Abstract 1236: Preclinical characterization of LY3484356, a novel, potent and orally bioavailable selective estrogen receptor degrader (SERD). Cancer Res 2021; 81 (13) 1236
- 65 Lim E, Beeram M, Prawira A. et al. Abstract OT‑09-03: EMBER: A phase 1a/b trial of LY3484356, a novel, oral selective estrogen-receptor degrader (SERD), in advanced ER+ breast cancer and endometroid endometrial cancer. Cancer Res 2021; 81 (04) OT‑09-03
- 66 Jhaveri KL, Lim E, Hamilton EP. et al. A first-in-human phase 1a/b trial of LY3484356, an oral selective estrogen receptor (ER) degrader (SERD) in ER+ advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Results from the EMBER study. J Clin Oncol 2021; 39 (15) 1050
- 67 Samatar AA, Li J, Hegde S. et al. Abstract 4373: Discovery of ZN‑c5, a novel potent and oral selective estrogen receptor degrader. Cancer Res 2020; 80 (16) 4373
- 68 Osborne C, Richards DA, Wilks ST. et al. Abstract PS11-26: A phase 1 study of D-0502, an orally bioavailable SERD, for advanced or metastatic HR-positive and HER2-negative breast cancer. Cancer Res 2021; 81 (04) PS11-26
- 69 Hamilton EP, Wang JS, Pluard T. et al. Abstract PD8-06: Phase I/II trial of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium, San Antonio, TX, USA. December 8-11 2020; DOI: 10.1158/1538-7445.SABCS20-PD8-06.