Next generation antibody-drug conjugates in the treatment of HER2-positive metastatic breast cancer: literature review and clinical case demonstration.
https://doi.org/10.62546/3034-1477-2024-2-3-70-78
Abstract
Breast cancer, along with its high incidence, is characterized by an extreme degree of tumor heterogeneity, which is reflected in the presence of molecular genetic classification and treatment algorithms based on immunohistochemical and mutational characteristics of the tumor. The revolution in the treatment of the HER2-positive subtype occurred about 25 years ago, when the first targeted drug trastuzumab came to clinical practice. Currently, there are a large number of treatment options for this subtype of breast cancer, including the most advanced drugs such as monoclonal antibody + cytotoxic agent conjugates. Trastuzumab deruxtecan is a new generation antibody–drug conjugate that has been registered in Russia and other countries as the therapy of choice in 2 and subsequent treatment lines for metastatic HER2-positive breast cancer. The article presents randomized clinical trials that formed the basis of these indications, and a phase IIIb/IV study DESTINY-Breast12 demonstrating high intracranial activity of this drug. The clinical case illustrates the effectiveness of trastuzumab deruxtecan in a late line in a pretreated patient with multiple metastasis including brain, as well as the possibility of diagnosing and correcting a specific adverse event such as interstitial lung disease.
Supporting agencies: The article was prepared without sponsorship.
About the Authors
M. I. Gluzma
St. Petersburg State University; St. Petersburg City Clinical Oncology Dispensary
Russian Federation
Russian Federation
Gluzman Mark Igorevich
7/9 Universitetskaya Emb., 199034; 56 Veteranov Ave., St. Petersburg 193318
I. O. Sharvashidze
St. Petersburg City Clinical Oncology Dispensary
Russian Federation
Russian Federation
56 Veteranov Ave., St. Petersburg 193318
References
1. International Agency for Research on Cancer. Cancer today (https://gco.iarc.fr/today/home).
2. National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Cancer stat facts: female breast cancer. 2021 (https://seer.cancer.gov/statfacts/html/breast.html).
3. Harbeck N., Penault-Llorca F., Cortes J. et al. Breast cancer // Nat. Rev. Dis. Primers. 2019. Vol. 5. Р. 66.ц
4. Cardoso F., Paluch-Shimon S., Senkus E. et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5) // Ann. Oncol. 2020. Vol. 31. Р. 1623–1649.
5. Baselga J., Cortés J., Kim S.-B. et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer // N. Engl. J. Med. 2012. Vol. 366. Р. 109–119.
6. Swain S.M., Baselga J., Kim S.-B. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer // N. Engl. J. Med. 2015. Vol. 372. Р. 724–734.
7. National Comprehensive Cancer Network. Breast cancer, version 1.2021. 2021 (https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf).
8. Verma S., Miles D., Gianni L. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer // N. Engl. J. Med. 2012. Vol. 367. Р. 1783–1791.
9. Nakada T., Sugihara K., Jikoh T., Abe Y., Agatsuma T. The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy // Chem. Pharm. Bull (Tokyo). 2019. Vol. 67. Р. 173–185.
10. 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. Vol. 22. Р. 5097–5108.
11. Ogitani Y., Hagihara K., Oitate M., Naito H., Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity // Cancer Sci. 2016. Vol. 107. Р. 1039–1046.
12. Modi S., Saura C., Yamashita T. et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer // N. Engl. J. Med. 2020. Vol. 382. Р. 610–621.
13. Enhertu (fam-trastuzumab deruxtecannxki) for injection, for intravenous use: highlights of prescribing information. Basking Ridge, NJ: Daiichi Sankyo, 2021 (package insert) (https://www.accessdata.fda.gov/drugsatfda_docs/label/ 2021/761139s011lbl.pdf).
14. Enhertu for intravenous drip infusion 100 mg: prescribing information. Tokyo: Daiichi Sankyo, 2020 (package insert) (https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/430574_4291452D1029_1_04) (In Japanese).
15. European Medicines Agency. Enhertu trastuzumab deruxtecan: summary of opinion. London: European Medicines Agency, 2020 (https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-enhertu_en.pdf).
16. Saura C. et al. Trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer (MBC): Updated survival results from a phase II trial (DESTINY-Breast01); ESMO 2021. Poster 279P.
17. André F. et al. Trastuzumab deruxtecan versus treatment of physician’s choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial // Lancet. 2023. Vol. 401. Р. 1773–1785.
18. Krop I. et al. SABSC. 2022. December 6–10, 2022; Abstract #GS2-01, Oral presentation.
19. Modi S., Saura C., Yamashita T. et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer // N. Engl. J. Med. 2020. Vol. 382, No, 7. Р. 610–621.
20. Collins J. et al. A real-word study on prevalence of and outcomes related to brain metastases among patients with HER2-positive metastatic breast cancer (mBC). Poster #186P, Poster presented at ESMO Breast Cancer 2022, Berlin.
21. Клинические рекомендации МЗ РФ «Вторичное злокачественное новообразование головного мозга и мозговых оболочек». 2020. Электронный ресурс: https://cr.minzdrav.gov.ru/recomend/534 дата обращения 22.10.2024).
22. Hurvitz S.A. et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial // ESMO Open. 2024. Vol. 9, Issue 5.
23. Hurvitz S.A. et al. A pooled analysis of Trastuzumab Deruxtecan in patients with HER2-positive metastatic breast cancer with brain metastases (BMs) from DESTINY-Breast01, -02, and -03 // Annals of Oncology. 2023. Vol. 34, Suppl. 2. P. S335–S336.
24. Harbeck N., Ciruelos E., Jerusalem G. et al. Trastuzumab deruxtecan in HER2-positive advanced/metastatic breast cancer with or without brain metastases: primary results from the phase 3b/4 DESTINY-Breast12 study // Nat. Med. 2024. Sep. 13. doi: 10.1038/s41591-024-03261-7.
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For citations:
Gluzma M.I., Sharvashidze I.O. Next generation antibody-drug conjugates in the treatment of HER2-positive metastatic breast cancer: literature review and clinical case demonstration. Clinical Case in Oncology. 2024;2(3):70-78. (In Russ.) https://doi.org/10.62546/3034-1477-2024-2-3-70-78
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