Advances in Antibody-Drug Conjugates in the Treatment of HER2-Positive Breast Cancer

References

• Sung H, Ferlay J, Siegel RL., et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660
   PubMed Web of Science ®Google Scholar
• Maomao C, He L, Dianqin S, et al. Current cancer burden in China: epidemiology, etiology, and prevention. Cancer Biol Med. 2022;19:8.
   Web of Science ®Google Scholar
• Majumder A, Sandhu M, Banerji D, Steri V, Olshen A, Moasser MM. The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers. Sci Rep. 2021;11(1):9091. doi:10.1038/s41598-021-88683-w
   PubMed Web of Science ®Google Scholar
• Ruiz-Saenz A, Dreyer C, Campbell MR, Steri V, Gulizia N, Moasser MM. HER2 Amplification in Tumors Activates PI3K/Akt Signaling Independent of HER3. Cancer Res. 2018;78(13):3645–3658. doi:10.1158/0008-5472.CAN-18-0430
   PubMed Web of Science ®Google Scholar
• Shui R, Liang X, Li X, et al. Hormone Receptor and Human Epidermal Growth Factor Receptor 2 Detection in Invasive Breast Carcinoma: a Retrospective Study of 12,467 Patients From 19 Chinese Representative Clinical Centers. Clin Breast Cancer. 2020;20(1):e65–e74. doi:10.1016/j.clbc.2019.07.013
   PubMed Web of Science ®Google Scholar
• Qin T, Yuan Z, Peng R, et al. HER2-positive breast cancer patients receiving trastuzumab treatment obtain prognosis comparable with that of HER2-negative breast cancer patients. Onco Targets Ther. 2013;6:341–347. doi:10.2147/OTT.S40851
   PubMed Web of Science ®Google Scholar
• Ishii K, Morii N, Yamashiro H. Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy. Core Evid. 2019;14:51–70. doi:10.2147/CE.S217848
   PubMed Web of Science ®Google Scholar
• Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol. 2010;28(1):92–98. doi:10.1200/JCO.2008.19.9844
   PubMed Web of Science ®Google Scholar
• Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195–1205. doi:10.1016/S0140-6736(16)32616-2
   PubMed Web of Science ®Google Scholar
• Xu B, Yan M, Ma F, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(3):351–360. doi:10.1016/S1470-2045(20)30702-6
   PubMed Web of Science ®Google Scholar
• Pernas S, Tolaney SM. HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance. Ther Adv Med Oncol. 2019;11:1758835919833519. doi:10.1177/1758835919833519
   Web of Science ®Google Scholar
• Nielsen KV, Jørgensen JT, Schønau A, Oster A. Human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131(9):1330. doi:10.5858/2007-131-1330a-HEGFRT
   PubMed Web of Science ®Google Scholar
• Uhlén M, Fagerberg L, Hallström BM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419. doi:10.1126/science.1260419
   PubMed Web of Science ®Google Scholar
• Lambert JM, Chari RV. Ado-trastuzumab Emtansine (T-DM1): an antibody-drug conjugate (ADC) for HER2-positive breast cancer. J Med Chem. 2014;57(16):6949–6964.
   PubMed Web of Science ®Google Scholar
• Krop IE, Beeram M, Modi S, et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol. 2010;28(16):2698–2704. doi:10.1200/JCO.2009.26.2071
   PubMed Web of Science ®Google Scholar
• Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Research. 2014;16(2):209. doi:10.1186/bcr3621
   PubMed Web of Science ®Google Scholar
• Diéras V, Miles D, Verma S, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732–742. doi:10.1016/S1470-2045(17)30312-1
   PubMed Web of Science ®Google Scholar
• Krop IE, Kim SB, González-Martín A, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(7):689–699. doi:10.1016/S1470-2045(14)70178-0
   PubMed Web of Science ®Google Scholar
• Perez EA, Barrios C, Eiermann W, et al. Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: primary Results From the Phase III MARIANNE Study. J Clin Oncol. 2017;35(2):141–148. doi:10.1200/JCO.2016.67.4887
   PubMed Web of Science ®Google Scholar
• Krop IE, LoRusso P, Miller KD, et al. A Phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2012;30(26):3234–3241. doi:10.1200/JCO.2011.40.5902
   PubMed Web of Science ®Google Scholar
• Burris HA 3rd, Rugo HS, Vukelja SJ, et al. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol. 2011;29(4):398–405. doi:10.1200/JCO.2010.29.5865
   PubMed Web of Science ®Google Scholar
• von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617–628. doi:10.1056/NEJMoa1814017
   PubMed Web of Science ®Google Scholar
• Raedler LA. Kadcyla (Ado-trastuzumab Emtansine): first Antibody-Drug Conjugate Approved for the Treatment of HER2-Positive Metastatic Breast Cancer. J Med. 2022;1:545.
   Google Scholar
• Pegram MD, Miles D, Tsui CK, Zong Y. HER2-Overexpressing/Amplified Breast Cancer as a Testing Ground for Antibody-Drug Conjugate Drug Development in Solid Tumors. Clin Cancer Res. 2020;26(4):775–786. doi:10.1158/1078-0432.CCR-18-1976
   PubMed Web of Science ®Google Scholar
• Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006;6(10):789–802. doi:10.1038/nrc1977
   PubMed Web of Science ®Google Scholar
• Perez J, Garrigós L, Gion M, et al. Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. Expert Opin Biol Ther. 2021;21(7):811–824. doi:10.1080/14712598.2021.1890710
   PubMed Web of Science ®Google Scholar
• Xu Z, Guo D, Jiang Z, et al. Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985). Eur J Med Chem. 2019;183:111682. doi:10.1016/j.ejmech.2019.111682
   PubMed Web of Science ®Google Scholar
• 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(20):5097–5108. doi:10.1158/1078-0432.CCR-15-2822
   PubMed Web of Science ®Google Scholar
• 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;67(3):173–185. doi:10.1248/cpb.c18-00744
   PubMed Web of Science ®Google Scholar
• Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, Phase 1 study. Lancet Oncol. 2019;20(6):816–826. doi:10.1016/S1470-2045(19)30097-X
   PubMed Web of Science ®Google Scholar
• Modi S, Park H, Murthy RK, et al. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: results From a Phase Ib Study. J Clin Oncol. 2020;38(17):1887–1896. doi:10.1200/JCO.19.02318
   PubMed Web of Science ®Google Scholar
• Saura Manich C, Modi S, Krop I, et al. 279P Trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer (MBC): updated survival results from a phase II trial (DESTINY-Breast01). Ann Oncol. 2021;32:S485–S486. doi:10.1016/j.annonc.2021.08.562
   Web of Science ®Google Scholar
• 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(4_Supplement):PD3-06-PD03–06.
   Web of Science ®Google Scholar
• Mode D, Stockholm LC. AstraZeneca: enhertu continues to demonstrate durable responses with new data from DESTINY-Breast01 in HER2-positive metastatic breast cancer. Cancer Res. 2021;81(4_Supplement):PD3-07-PD03–07.
   Google Scholar
• Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022;386(12):1143–1154. doi:10.1056/NEJMoa2115022
   PubMed Web of Science ®Google Scholar
• Hurvitz S, Kim S-B, Chung W-P, et al. Abstract GS3-01: trastuzumab deruxtecan (T-DXd; DS-8201a) vs. trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Cancer Res. 2022;82(4_Supplement):GS3-01-GS03–01. doi:10.1158/1538-7445.SABCS21-GS3-01
   Web of Science ®Google Scholar
• Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9–20. doi:10.1056/NEJMoa2203690
   PubMed Web of Science ®Google Scholar
• Hamilton E, Shapiro CL, Petrylak D, et al. Abstract PD3-07: trastuzumab deruxtecan (T-DXd; DS-8201) with nivolumab in patients with HER2-expressing, advanced breast cancer: a 2-part, phase 1b, multicenter, open-label study. Cancer Res. 2021;81(4_Supplement):PD3-07-PD03–07.
   Web of Science ®Google Scholar
• Schmid P, Im S-A, Armstrong A, et al. BEGONIA: phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC)—Initial results from arm 1, d+paclitaxel (P), and arm 6, d+trastuzumab deruxtecan (T-DXd). J Clin Oncol. 2021;39(15_suppl):1023. doi:10.1200/JCO.2021.39.15_suppl.1023
   Web of Science ®Google Scholar
• Linehan AS, Fitzpatrick OM, Morris PG. Profile of Trastuzumab Deruxtecan in the Management of Patients with HER2-Positive Unresectable or Metastatic Breast Cancer: an Evidence-Based Review. Breast Cancer. 2021;13:151–159. doi:10.2147/BCTT.S245024
   PubMed Web of Science ®Google Scholar
• Anders CK, LeBoeuf NR, Bashoura L, Faiz SA, Shariff AI, Thomas A, What’s the Price? Toxicities of Targeted Therapies in Breast Cancer Care. Am Soc Clin Oncol Educ Book. 2020;40:55–70. doi:10.1200/EDBK_279465
   PubMedGoogle Scholar
• Elgersma RC, Coumans RGE, Huijbregts T, et al. Design, Synthesis, and Evaluation of Linker-Duocarmycin Payloads: toward Selection of HER2-Targeting Antibody–Drug Conjugate SYD985. Mol Pharm. 2015;12(6):1813–1835. doi:10.1021/mp500781a
   PubMed Web of Science ®Google Scholar
• Dokter W, Ubink R, van der Lee M, et al. Preclinical profile of the HER2-targeting ADC SYD983/SYD985: introduction of a new duocarmycin-based linker-drug platform. Mol Cancer Ther. 2014;13(11):2618–2629. doi:10.1158/1535-7163.MCT-14-0040-T
   PubMed Web of Science ®Google Scholar
• Saura C, Thistlethwaite F, Banerji U, et al. A phase I expansion cohorts study of SYD985 in heavily pretreated patients with HER2-positive or HER2-low metastatic breast cancer. J Clin Oncol. 2018;36(15_suppl):1014. doi:10.1200/JCO.2018.36.15_suppl.1014
   Web of Science ®Google Scholar
• Nadal-Serrano M, Morancho B, Escrivá-de-Romaní S, et al. The Second Generation Antibody-Drug Conjugate SYD985 Overcomes Resistances to T-DM1. Cancers. 2020;12:3. doi:10.3390/cancers12030670
   Web of Science ®Google Scholar
• Saura Manich C, O’Shaughnessy J, Aftimos PG, et al. LBA15 Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer. Ann Oncol. 2021;32:S1288. doi:10.1016/j.annonc.2021.08.2088
   Web of Science ®Google Scholar
• Bergstrom D, Bodyak N, Park P, et al. Abstract P4-14-28: XMT-1522 induces tumor regressions in pre-clinical models representing HER2-positive and HER2 low-expressing breast cancer. Cancer Res. 2016;76(4_Supplement):P4-14-28-P14-14–28. doi:10.1158/1538-7445.SABCS15-P4-14-28
   Web of Science ®Google Scholar
• Hamilton EP, Barve MA, Bardia A, et al. Phase 1 dose escalation of XMT-1522, a novel HER2-targeting antibody-drug conjugate (ADC), in patients (pts) with HER2-expressing breast, lung and gastric tumors. J Clin Oncol. 2018;36(15_suppl):2546. doi:10.1200/JCO.2018.36.15_suppl.2546
   Web of Science ®Google Scholar
• Le Joncour V, Martins A, Puhka M, et al. A Novel Anti-HER2 Antibody-Drug Conjugate XMT-1522 for HER2-Positive Breast and Gastric Cancers Resistant to Trastuzumab Emtansine. Mol Cancer Ther. 2019;18(10):1721–1730. doi:10.1158/1535-7163.MCT-19-0207
   PubMed Web of Science ®Google Scholar
• Liu Y, Lian W, Zhao X, et al. A first in-human study of A166 in patients with locally advanced/metastatic solid tumors which are HER2-positive or HER2-amplified who did not respond or stopped responding to approved therapies. J Clin Oncol. 2020;38(15_suppl):1049. doi:10.1200/JCO.2020.38.15_suppl.1049
   Web of Science ®Google Scholar
• Liu Y, Lian W, Zhao X, et al. A phase I study of safety and pharmacokinetics of A166, a novel selective inhibitor of human epidermal growth factor receptor-2 in Chinese patients with advanced solid tumors. J Clin Oncol. 2020;38(15_suppl):e13007. doi:10.1200/JCO.2020.38.15_suppl.e13007
   Web of Science ®Google Scholar
• Wang J, Xu B, Wang W, Fang J. An open-label, dose-escalation phase I study to evaluate RC48-ADC, a novel antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer. J Clin Oncol. 2018;36(15_suppl):1030. doi:10.1200/JCO.2018.36.15_suppl.1030
   Web of Science ®Google Scholar
• Xu B, Wang J, Zhang Q, et al. An open-label, multicenter, phase Ib study to evaluate RC48-ADC in patients with HER2-positive metastatic breast cancer. J Clin Oncol. 2018;36(15_suppl):1028. doi:10.1200/JCO.2018.36.15_suppl.1028
   Web of Science ®Google Scholar
• LoRusso P, Krop I, Miller K, et al. Abstract CT234: a phase I study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2+ metastatic breast cancer. Cancer Res. 2015;75(15_Supplement):CT234. doi:10.1158/1538-7445.AM2015-CT234
   Web of Science ®Google Scholar
• Miller K, Cortes J, Hurvitz SA, et al. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer. BMC Cancer. 2016;16:352. doi:10.1186/s12885-016-2385-z
   PubMed Web of Science ®Google Scholar
• Li J, Toader D, Perry SR, et al. Abstract 2970: MEDI4276, a HER2-targeting antibody tubulysin conjugate, displays potent in vitro and in vivo activity in preclinical studies. Cancer Res. 2016;76(14_Supplement):2970. doi:10.1158/1538-7445.AM2016-2970
   Web of Science ®Google Scholar
• Pegram MD, Hamilton EP, Tan AR, et al. First-in-Human, Phase 1 Dose-Escalation Study of Biparatopic Anti-HER2 Antibody–Drug Conjugate MEDI4276 in Patients with HER2-positive Advanced Breast or Gastric Cancer. Mol Cancer Ther. 2021;20(8):1442–1453. doi:10.1158/1535-7163.MCT-20-0014
   PubMed Web of Science ®Google Scholar
• Meric-Bernstam F, Calvo E, Moreno V, et al. A phase I dose escalation study evaluating the safety and tolerability of a novel anti-HER2 antibody-drug conjugate (PF-06804103) in patients with HER2-positive solid tumors. J Clin Oncol. 2020;38(15_suppl):1039. doi:10.1200/JCO.2020.38.15_suppl.1039
   Web of Science ®Google Scholar
• Barok M, Le Joncour V, Martins A, et al. ARX788, a novel anti-HER2 antibody-drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer. Cancer Lett. 2020;473:156–163. doi:10.1016/j.canlet.2019.12.037
   PubMed Web of Science ®Google Scholar
• Hu X, Zhang J, Ji D, et al. Abstract P1-18-16: a phase 1 study of ARX788, a HER2-targeting antibody-drug conjugate, in patients with metastatic HER2-positive breast cancer. Cancer Res. 2020;80(4_Supplement):P1-18-16-P11-18–16.
   Web of Science ®Google Scholar
• Rinnerthaler G, Gampenrieder SP, Greil R. HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer. Int J Mol Sci. 2019;20:5. doi:10.3390/ijms20051115
   Web of Science ®Google Scholar
• Park YH, Ahn HK, Kim J-Y, et al. First-in-human phase I study of ALT-P7, a HER2-targeting antibody-drug conjugate in patients with HER2-positive advanced breast cancer. J Clin Oncol. 2020;38(15_suppl):3551. doi:10.1200/JCO.2020.38.15_suppl.3551
   Google Scholar
• Hong R, Xia W, Wang L, et al. Safety, tolerability, and pharmacokinetics of BAT8001 in patients with HER2-positive breast cancer: an open-label, dose-escalation, phase I study. Cancer Commun. 2021;41(2):171–182. doi:10.1002/cac2.12135
   PubMed Web of Science ®Google Scholar
• Chen Daniel S, Mellman I. Oncology Meets Immunology: the Cancer-Immunity Cycle. Immunity. 2013;39(1):1–10. doi:10.1016/j.immuni.2013.07.012
   PubMed Web of Science ®Google Scholar
• Gatti-Mays ME, Balko JM, Gameiro SR, et al. If we build it they will come: targeting the immune response to breast cancer. Npj Breast Cancer. 2019;5(1):37. doi:10.1038/s41523-019-0133-7
   PubMed Web of Science ®Google Scholar
• Müller P, Kreuzaler M, Khan T, et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci Transl Med. 2015;7(315):315ra188. doi:10.1126/scitranslmed.aac4925
   PubMed Web of Science ®Google Scholar
• Waks AG, Keenan T, Li T, et al. A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC). J Clin Oncol. 2020;38(15_suppl):1046. doi:10.1200/JCO.2020.38.15_suppl.1046
   Web of Science ®Google Scholar
• Hamilton EP, Kaklamani V, Falkson C, et al. Abstract PD1-05: atezolizumab in combination with trastuzumab emtansine or with trastuzumab and pertuzumab in patients with HER2-positive breast cancer and atezolizumab with doxorubicin and cyclophosphamide in HER2-negative breast cancer: safety and biomarker outcomes from a multi-cohort Phase Ib study. Cancer Res. 2020;80(4_Supplement):PD1-05-PD01–05.
   Web of Science ®Google Scholar
• Emens LA, Esteva FJ, Beresford M, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol. 2020;21(10):1283–1295. doi:10.1016/S1470-2045(20)30465-4
   PubMed Web of Science ®Google Scholar
• Loi S, Schneeweiss A, Song E, et al. 329TiP KATE3: a phase III study of trastuzumab emtansine (T-DM1) in combination with atezolizumab or placebo in patients with previously treated HER2-positive and PD-L1–positive locally advanced or metastatic breast cancer. Ann Oncol. 2021;32:S509. doi:10.1016/j.annonc.2021.08.612
   Web of Science ®Google Scholar
• Borghaei H, Besse B, Bardia A, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with pembrolizumab in patients with advanced/metastatic breast or non-small cell lung cancer (NSCLC): a phase Ib, multicenter, study. J Clin Oncol. 2020;38(15_suppl):TPS1100.
   Web of Science ®Google Scholar
• Huang L, Wang R, Xie K, et al. A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+ tumors in hPD-1 transgenic mouse model and contributes immune memory formation. Breast Cancer Res Treat. 2022;191(1):51–61. doi:10.1007/s10549-021-06384-4
   PubMed Web of Science ®Google Scholar
• Ackerman SE, Pearson CI, Gregorio JD, et al. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Nature Cancer. 2021;2(1):18–33. doi:10.1038/s43018-020-00136-x
   PubMedGoogle Scholar
• Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20(6):816–826.
   PubMed Web of Science ®Google Scholar
• Hamilton E, Shapiro CL, Petrylak D, et al. Abstract PD3-07: trastuzumab deruxtecan (T-DXd; DS-8201) with nivolumab in patients with HER2-expressing, advanced breast cancer: a 2-part, phase 1b, multicenter, open-label study. Cancer Research. 2021;81(4_Supplement):PD3-07-PD3–07. doi:10.1158/1538-7445.SABCS20-PD3-07
   Web of Science ®Google Scholar
• Manich CS, Modi S, Krop I, et al. 279P trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer (MBC): updated survival results from a phase II trial (DESTINY-Breast01). Ann Oncol. 2021;32:S485–S486.
   Web of Science ®Google Scholar
• André F, Shahidi J, Lee C, Wang K, Krop IE. Abstract OT1-07-04:[Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) vs investigator’s choice of treatment in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1: a randomized, phase 3 trial (DESTINY-Breast02). Cancer Res. 2020;80(4_Supplement):OT1. AACR.
   Web of Science ®Google Scholar
• Lézard L. ENHERTU® Significantly Improved Progression-Free Survival in DESTINY-Breast03 Head-to-Head Trial Versus Trastuzumab Emtansine (T-DM1) in Patients with HER2 Positive Metastatic Breast Cancer. Cancer Res;2021;1:463.
   Google Scholar
• 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:S1287–S1288. doi:10.1016/j.annonc.2021.08.2087
   Web of Science ®Google Scholar
• Modi S, Ohtani S, Lee C, Wang Y, Saxena K, Cameron DA. Abstract OT1-07-02: a phase 3, multicenter, randomized, open-label trial of [fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) vs investigator’s choice in HER2-low breast cancer (DESTINY-Breast04). Cancer Research. 2020;80(4_Supplement):OT1-07-02-OT1-07–02. doi:10.1158/1538-7445.SABCS19-OT1-07-02
   Web of Science ®Google Scholar
• Geyer CE, Untch M, Prat A, et al. Abstract OT-03-01: trastuzumab deruxtecan (T-DXd; DS-8201) vs trastuzumab emtansine (T-DM1) in high-risk patients with HER2-positive, residual invasive early breast cancer after neoadjuvant therapy: a randomized, phase 3 trial (DESTINY-Breast05). Cancer Research. 2021;81(4_Supplement):OT-03-01-OT-03–01. doi:10.1158/1538-7445.SABCS20-OT-03-01
   Web of Science ®Google Scholar
• Hurvitz SA, Peddi PF, Tetef ML, et al. TRIO-US B-12 TALENT: Phase II Neoadjuvant Trial Evaluating Trastuzumab Deruxtecan with or Without Anastrozole for HER2-Low,HR+ Early Stage Breast Cancer. Wolters Kluwer Health; 2021.
   Google Scholar
• Bardia A, Barrios C, Dent R, et al. Abstract OT-03-09: trastuzumab deruxtecan (T-DXd; DS-8201) vs investigator’s choice of chemotherapy in patients with hormone receptor-positive (HR+), HER2 low metastatic breast cancer whose disease has progressed on endocrine therapy in the metastatic setting: a randomized, global phase 3 trial (DESTINY-Breast06). Cancer Res. 2021;81(4_Supplement):OT.
   Web of Science ®Google Scholar
• Andre F, Hamilton EP, Loi S, et al. Trastuzumab Deruxtecan (T-Dxd) Combinations in Patients with HER2-Positive Advanced or Metastatic Breast Cancer: A Phase 1b/2, Open-Label, Multicenter, Dose-Finding and Dose-Expansion Study (DESTINY-Breast07). Wolters Kluwer Health; 2021.
   Google Scholar
• Jhaveri K, Hamilton E, Loi S, et al. Abstract OT-03-05: trastuzumab deruxtecan (T-DXd; DS-8201) in combination with other anticancer agents in patients with HER2-low metastatic breast cancer: a phase 1b, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast08). Cancer Res. 2021;81(4_Supplement):OT.
   Web of Science ®Google Scholar
• Tolaney S, Barroso-Sousa R, Jiang Z, et al. 328TiP Phase III study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09. Ann Oncol. 2021;32:S507–S508. doi:10.1016/j.annonc.2021.08.611
   Web of Science ®Google Scholar
• Bartsch R, Berghoff A, Furtner J, et al. 280P Intracranial activity of trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients with active brain metastases: results from the first stage of the phase II TUXEDO-1 trial. Ann Oncol. 2021;32:S486. doi:10.1016/j.annonc.2021.08.563
   Web of Science ®Google Scholar
• Batista MV, Pérez-Garcia J, Cussac AL, et al. 330TiP Trastuzumab deruxtecan (T-DXd; DS-8201) in HER2-positive (HER2+) and HER2-low expressing (HER-LE) metastatic breast cancer (MBC) with brain metastases (BM) and/or leptomeningeal carcinomatosis (LMC): DEBBRAH. Ann Oncol. 2021;32:S509–S510. doi:10.1016/j.annonc.2021.08.613
   Web of Science ®Google Scholar
• Krop IE, Ramos J, Zhang C, Hamilton EP. HER2CLIMB-04: Phase 2 Open Label Trial of Tucatinib Plus Trastuzumab Deruxtecan in Patients with HER2+ Unresectable Locally Advanced or Metastatic Breast Cancer with and without Brain Metastases (Trial in Progress). Wolters Kluwer Health; 2021.
   Google Scholar
• Borghaei H, Besse B, Bardia A, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with pembrolizumab in patients with advanced/metastatic breast or non-small cell lung cancer (NSCLC): a phase Ib, multicenter, study. Am Soc Clin Oncol. 2020;38(15_suppl):TPS1100–TPS1100. doi:10.1200/JCO.2020.38.15_suppl.TPS1100
   Web of Science ®Google Scholar
• Prat A, Gavilá J, Pernas S, et al. Abstract OT-03-07: solti-1804 HER2-PREDICT: a biomarker research study of DS8201-A-U301-U302 and-U303 trials. Cancer Research. 2021;81(4_Supplement):OT-03-07-OT-03–07. doi:10.1158/1538-7445.SABCS20-OT-03-07
   Web of Science ®Google Scholar
• Shen B-Q, Bumbaca D, Saad O, et al. Catabolic Fate and Pharmacokinetic Characterization of Trastuzumab Emtansine (T-DM1): an Emphasis on Preclinical and Clinical Catabolism. Curr Drug Metab. 2012;13(7):901–910. doi:10.2174/138920012802138598
   PubMed Web of Science ®Google Scholar
• Krop IE, Saura C, Yamashita T, et al. Abstract GS1-03: [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) in subjects with HER2-positive metastatic breast cancer previously treated with T-DM1: a phase 2, multicenter, open-label study (DESTINY-Breast01). Cancer Res. 2020;80(4_Supplement):GS1-03-GS01–03. doi:10.1158/1538-7445.SABCS19-GS1-03
   Web of Science ®Google Scholar
• Faria M, Peay M, Lam B, et al. Multiplex LC-MS/MS Assays for Clinical Bioanalysis of MEDI4276, an Antibody-Drug Conjugate of Tubulysin Analogue Attached via Cleavable Linker to a Biparatopic Humanized Antibody against HER-2. Antibodies. 2019;8(1):11. doi:10.3390/antib8010011
   Web of Science ®Google Scholar
• Graziani EI, Sung M, Ma D, et al. PF-06804103, A Site-specific Anti-HER2 Antibody–Drug Conjugate for the Treatment of HER2-expressing Breast, Gastric, and Lung Cancers. Mol Cancer Ther. 2020;19(10):2068–2078. doi:10.1158/1535-7163.MCT-20-0237
   PubMed Web of Science ®Google Scholar
• Nagaraja Shastri P, Zhu J, Skidmore L, et al. Nonclinical Development of Next-generation Site-specific HER2-targeting Antibody–drug Conjugate (ARX788) for Breast Cancer Treatment. Mol Cancer Ther. 2020;19(9):1822–1832. doi:10.1158/1535-7163.MCT-19-0692
   PubMed Web of Science ®Google Scholar
• Krop I, Hamilton E, Jung KH, et al. Abstract P2-13-25: a phase I dose-escalation study of DHES0815A, a HER2-targeting antibody-drug conjugate with a DNA monoalkylator payload, in patients with HER2-positive breast cancer. Cancer Res. 2022;82(4_Supplement):P2-13-25-P12-13–25. doi:10.1158/1538-7445.SABCS21-P2-13-25
   Web of Science ®Google Scholar