Update Breast Cancer 2022 Part 2 – Advanced Stage Breast Cancer

Abstract

For patients with advanced breast cancer, several novel therapies have emerged in recent years, including CDK4/6 inhibitors, immune checkpoint inhibitors, PARP inhibitors, alpelisib, tucatinib and trastuzumab-deruxtecan, and sacituzumab-govitecan, which have transformed and expanded the therapeutic landscape for patients with advanced breast cancer. Some of these substances have now been approved for use in the early stages of the disease, or are expected to be approved in the near future, so the therapeutic landscape will change once again. Therefore, current scientific efforts are focused on the introduction of new substances and understanding their mechanisms of progression and efficacy. This review summarizes recent developments with reference to recent publications and conferences. Findings on the treatment of patients with HER2-positive breast cancer and brain metastases are presented, as are a number of studies looking at biomarkers in patients with HER2-negative, hormone receptor-positive breast cancer. In particular, the introduction of oral selective estrogen receptor degraders provides new opportunities to establish biomarker-based therapy. Molecular diagnostics is establishing itself as a diagnostic marker and parameter of progression.

Key words

breast cancer - metastatic - biomarker - PD-L1 - ADC

Publikationsverlauf

Eingereicht: 21. März 2022

Angenommen nach Revision: 26. März 2022

Artikel online veröffentlicht:
03. Juni 2022

• References/Literatur

• 1 Brett JO, Spring LM, Bardia A. et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res 2021; 23: 85
• 2 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
• 3 OʼLeary B, Cutts RJ, Liu Y. et al. The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial. Cancer Discov 2018; 8: 1390-1403
• 4 Bidard F, Hardy-Bessard A, Bachelot T. et al. Fulvestrant-palbociclib vs. continuing aromatase inhibitor-palbociclib upon detection of circulating ESR1 mutation in HR+ HER2- metastatic breast cancer patients: Results of PADA-1, a UCBG-GINECO randomized phase 3 trial. San Antonio Breast Cancer Symposium 2021; 2021: GS3-05
• 5 clinicaltrials.gov. Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (SERENA-6). 2021. Accessed October 24, 2021 at: https://clinicaltrials.gov/ct2/show/NCT04964934
• 6 Lüftner D, Schütz F, Stickeler E. et al. Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2022;
• 7 Nabieva N, Haberle L, Brucker SY. et al. Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients. Int J Cancer 2019; 145: 2114-2121
• 8 Bardia A, Neven P, Streich G. et al. Elacestrant, an oral selective estrogen receptor degrader (SERD), vs. investigatorʼs choice of endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial. San Antonio Breast Cancer Symposium 2021; 2021: GS2-02
• 9 European Medicines Agency. Summary of product characteristics (SmPC). 2022. Accessed March 26, 2022 at: https://www.ema.europa.eu/en/documents/product-information/verzenios-epar-product-information_en.pdf
• 10 Collins JM, Nordstrom BL, McLaurin KK. et al. A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status. Oncol Ther 2021;
• 11 Fasching PA, Yadav S, Hu C. et al. Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer-Association With Patient and Disease Characteristics and Effect on Prognosis. J Clin Oncol 2021; 39: 1619-1630
• 12 Hortobagyi GN, Stemmer SM, Burris HA. et al. 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 L) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol 2021; 32: S1290-S1291
• 13 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
• 14 Hortobagyi GN, Stemmer SM, Burris HA. et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol 2018; 29: 1541-1547
• 15 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
• 16 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;
• 17 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
• 18 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
• 19 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;
• 20 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;
• 21 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
• 22 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
• 23 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
• 24 Finn RS, Martin M, Rugo HS. et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375: 1925-1936
• 25 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
• 26 Turner NC, Ro J, Andre F. et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209-219
• 27 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
• 28 Schneeweiss A, Ettl J, Luftner D. et al. Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer – Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany. Breast 2020; 54: 88-95
• 29 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
• 30 Bianchini G, Malorni L, Arpino G. et al. Circulating tumor DNA (ctDNA) dynamics in patients with hormone receptor positive (HR+)/HER2 negative (HER2-) advanced breast cancer (aBC) treated in first line with ribociclib (R) and letrozole (L) in the BioItaLEE trial. San Antonio Breast Cancer Symposium 2021; 2021: GS3-07
• 31 André F, Gonçalves A, Filleron T. et al. Clinical utility of molecular tumor profiling: Results from the randomized trial SAFIR02-BREAST. San Antonio Breast Cancer Symposium 2021; 2021: GS1-10
• 32 Mateo J, Chakravarty D, Dienstmann R. et al. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 2018; 29: 1895-1902
• 33 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
• 34 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
• 35 Cortes J, Cescon DW, Rugo HS. et al. Final results of KEYNOTE-355: Randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs. placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. San Antonio Breast Cancer Symposium 2021; 2021: GS1-02
• 36 Bardia A, Hurvitz SA, Tolaney SM. et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021; 384: 1529-1541
• 37 Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget 2018; 9: 28989-29006
• 38 Zaman S, Jadid H, Denson AC. et al. Targeting Trop-2 in solid tumors: future prospects. Onco Targets Ther 2019; 12: 1781-1790
• 39 Vranic S, Gatalica Z. Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers. Bosn J Basic Med Sci 2022; 22: 14-21
• 40 Liao S, Wang B, Zeng R. et al. Recent advances in trophoblast cell-surface antigen 2 targeted therapy for solid tumors. Drug Dev Res 2021; 82: 1096-1110
• 41 Krop I, Juric D, Shimizu T. et al. Datopotamab deruxtecan in advanced/metastatic HER2- breast cancer: Results from the phase 1 TROPION-PanTumor01 study. San Antonio Breast Cancer Symposium 2021; 2021: GS1-05
• 42 Marme F. Phase-III-Studie zur postneoadjuvantenBehandlung mit dem Antikörper-Medikamenten-KonjugatSacituzumab Govitecan bei Frauen mit frühem, HER2-negativem Brustkrebs und hohem Rückfallrisiko nach einer Standardbehandlung im neoadjuvantenSetting -SASCIA. 2020. Accessed July 16, 2020 at: https://www.gbg.de/wAssets/docs/events-vortraege/2020_JT/23_SASCIA.pdf
• 43 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; 38: 2610-2619
• 44 Hurvitz S, Kim SB, Chung WP. et al. Trastuzumab deruxtecan vs. trastuzumab emtansine in patients with HER2+ metastatic breast cancer: Results of the randomized phase 3 study DESTINY-Breast03. San Antonio Breast Cancer Symposium 2021; 2021: GS3-01
• 45 Montemurro F, Delaloge S, Barrios CH. et al. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase III b clinical trial(). Ann Oncol 2020; 31: 1350-1358
• 46 clinicaltrials.gov. DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]. 2022. Accessed February 01, 2022 at: https://clinicaltrials.gov/ct2/show/NCT03529110
• 47 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
• 48 Liao S, Wang B, Zeng R. et al. Recent advances in trophoblast cell-surface antigen 2 targeted therapy for solid tumors. Preprints 2020;