Neue Antikörper-Wirkstoff-Konjugate in der klinischen Praxis zur Behandlung des metastatischen Brustkrebses: Therapie-Adhärenz, Wirksamkeit und Verträglichkeit – Real-World-Daten aus deutschen Brustkrebszentren

Zusammenfassung

Einleitung

Trastuzumab-Deruxtecan (T-DXd) und Sacituzumab-Govitecan (SG) sind Antikörper-Wirkstoff-Konjugate (ADCs) der 3. Generation, die vor Kurzem zur Behandlung des metastatischen Brustkrebses über mehrere Subtypen hinweg und in verschiedenen therapeutischen Zusammenhängen zugelassen wurden.

Material und Methoden

Ziel dieser retrospektiven multizentrischen Studie war es, die Real-World-Daten über die Verträglichkeit, Umsetzbarkeit und Wirksamkeit dieser Wirkstoffe in einer vorbehandelten Real-World-Kohorte in 3 großen deutschen Brustkrebszentren zu bewerten.

Ergebnisse

Eingeschlossen wurden 125 Patientinnen, die zwischen November 2020 und Juni 2023 mit T-DXd oder SG behandelt wurden (T-DXd: 77 Patientinnen; SG: 48 Patientinnen). Die mediane Behandlungsdauer betrug 6,0 Monate für eine T-DXd- und 3,5 Monate für eine SG-Therapie, mit einer medianen Nachbeobachtungszeit von 10,4 Monaten für T-DXd (95 %-KI: 8,4–11,6) und 11,8 Monaten für SG (95 %-KI: 8,0–14,4). 33,3 % der Patientinnen entwickelten eine schwere Neutropenie (CTC ≥ III°) im Verlauf der SG-Therapie, wobei eine numerische Reduktion nach dem primären prophylaktischen Einsatz von G-CSF beobachtet wurde. Bei 8 von 77 Patientinnen (10,4 %) trat eine T-DXd-bedingte Pneumonitis auf. Das mediane progressionsfreie Überleben (mPFÜ) betrug 8,6 Monate (95 %-KI: 5,8–12,4) mit T-DXd (HER2 +: 10,8; HER2-low: 4,7) und 4,9 Monate (95 %-KI: 2,8–6,3) mit SG (TNBC 4,9; HR+/HER2-: nicht erreicht). Das mediane Gesamtüberleben (GÜ) betrug 23,8 Monate (95 %-KI: 16,1–nicht schätzbar) mit einer T-DXd-Therapie (HER2 +: 27,1; HER2-low: nicht erreicht) und 12,4 Monate (95 %-KI: 8,7–nicht schätzbar) mit einer SG-Therapie (TNBC: 12,4, HR+/HER2-: nicht erreicht). Verabreicht wurden 95,7 % der im Protokoll vorgegebenen therapeutischen T-DXd-Dosis bzw. 89,6 % der vorgegebenen SG-Dosis.

Schlussfolgerung

Insgesamt weisen die Daten auf eine gute Umsetzbarkeit, Wirksamkeit und Verträglichkeit von ADC-Therapien in einer realen Umgebung hin.

Abstract

Introduction

The 3rd-generation antibody-drug conjugates (ADC), Trastuzumab Deruxtecan (T-DXd) and Sacituzumab/Govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts.

Materials and Methods

This retrospective, multi-centric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at 3 major German breast cancer centres.

Results

125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95 % CI: 8.4–11.6) and 11.8 months for SG (95 % CI: 8.0–14.4). Severe neutropenia (CTC ≥ III°) occurred in 33.3 % during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95 % CI: 5.8–12.4) with T-DXd (HER2 +: 10.8; HER2-low: 4.7) and 4.9 months (95 % CI: 2.8–6.3) with SG (TNBC 4.9; HR+/HER2-: not reached). Median overall survival (OS) was 23.8 months (95 % CI: 16.1–not estimable) with T-DXd (HER2 +: 27.1; HER2-low: not reached), and 12.4 months (95 % CI: 8.7–not estimable) with SG therapy (TNBC: 12.4, HR+/HER2-: not reached). 95.7 % of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6 % for SG.

Conclusion

Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting.

Publication History

Received: 11 May 2024

Accepted: 28 July 2024

Article published online:
11 June 2025

• Literatur

• 1 Arnold M, Morgan E, Rumgay H. et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 2022; 66: 15-23
• 2 Adams E, Wildiers H, Neven P. et al. Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody-drug conjugates in the breast cancer treatment landscape. ESMO Open 2021; 6: 100204
• 3 Hurvitz SA, Hegg R, Chung WP. et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, openlabel, phase 3 trial. Lancet 2023; 401: 105-117
• 4 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
• 5 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
• 6 Bardia A, Hurvitz SA, Tolaney SM. et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021; 384: 1529-1541
• 7 Starodub AN, Ocean AJ, Shah MA. et al. First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin Cancer Res 2015; 21: 3870-3878
• 8 Sharkey RM, McBride WJ, Cardillo TM. et al. Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-Trop-2-SN-38 Antibody Conjugate (Sacituzumab Govitecan). Clin Cancer Res 2015; 21: 5131-5138
• 9 Bardia A, Mayer IA, Vahdat LT. et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med 2019; 380: 741-751
• 10 Bardia A, Messersmith WA, Kio EA. et al. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Ann Oncol 2021; 32: 746-756
• 11 Bardia A, Rugo HS, Tolaney SM. et al. Final Results From the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression. J Clin Oncol 2024; 42: 1738-1744
• 12 European Medicines Agency. Trodelvy. Accessed December 30, 2023 at: https://www.ema.europa.eu/en/medicines/human/EPAR/trodelvy
• 13 U.S. Food & Drug Administration, (FDA). FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. Accessed December 30, 2023 at: https://www.fda.gov/drugs/resources-informationapproved-drugs/fda-grants-regular-approval-sacituzumab-govitecantriple-negative-breast-cancer
• 14 Kalinsky K, Diamond JR, Vahdat LT. et al. Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol 2020; 31: 1709-1718
• 15 Rugo HS, Bardia A, Marmé 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
• 16 Rugo HS, Bardia A, Marmé F. et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet 2023; 402: 1423-1433
• 17 Nakada T, Sugihara K, Jikoh T. et al. The Latest Research and Development into the Antibody-Drug Conjugate, [fam-] Trastuzumab Deruxtecan (DS-8201a), for HER2 Cancer Therapy. Chem Pharm Bull (Tokyo) 2019; 67: 173-185
• 18 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
• 19 Modi S, Saura C, Yamashita T. et al. Abstract PD3-06: Updated results from DESTINY-breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd) in HER2 positive metastatic breast cancer. Cancer Res 2021; 81: PD3-06
• 20 Cortés J, Kim S-B, Chung W-P. et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med 2022; 386: 1143-1154
• 21 Ogitani Y, Aida T, Hagihara K. et al. DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1. Clin Cancer Res 2016; 22: 5097-5108
• 22 Dannehl D, Jakob D, Mergel F. et al. The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients – a multicenter real-world analysis. ESMO Open 2024; 9: 102995
• 23 Schäffler H, Mergel F, Pfister K. et al. The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers. Int J Mol Sci 2023; 24: 16366
• 24 Dannehl D, Engler T, Volmer LL. et al. Which Patients Do We Need to Test for BRCA1/2 Mutation? Feasibility of Adjuvant Olaparib Treatment in Early Breast Cancer-Real-World Data from Two Large German Breast Centers. Cancers 2023; 15: 3847
• 25 Dannehl D, Volmer LL, Weiss M. et al. Feasibility of Adjuvant Treatment with Abemaciclib-Real-World Data from a Large German Breast Center. J Pers Med 2022; 12: 382
• 26 Shuster JJ. Median follow-up in clinical trials. J Clin Oncol 1991; 9: 191-192
• 27 Reinisch M, Bruzas S, Spoenlein J. et al. Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. Ther Adv Med Oncol 2023; 15
• 28 Carey LA, Loirat D, Punie K. et al. Sacituzumab govitecan as second-line treatment for metastatic triple-negative breast cancer-phase 3 ASCENT study subanalysis. NPJ Breast Cancer 2022; 8: 72
• 29 Botticelli A, Caputo R, Scagnoli S. et al. Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study. Oncologist 2024; 29: 303-310
• 30 Cardoso F, Senkus E, Costa A. et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)†. Ann Oncol 2018; 29: 1634-1657
• 31 Powell CA, Modi S, Iwata H. et al. Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open 2022; 7: 100554
• 32 Rugo HS, Bianchini G, Cortes J. et al. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open 2022; 7: 100553
• 33 Bardia A, Hu X, Dent R. et al. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med 2024; 391: 2110-2122