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Review

Trastuzumab-deruxtecan in solid tumors with HER2 alterations: from early phase development to the first agnostic approval of an antibody–drug conjugate

ORCID Icon & ORCID Icon
Pages 851-865 | Received 12 Apr 2024, Accepted 02 Jul 2024, Published online: 09 Jul 2024

References

  • Tarantino P, Pestana RC, Corti C, et al. Antibody-drug conjugates: smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 2022 Mar;72(2):165–182. doi: 10.3322/CAAC.21705
  • Ascione L, Crimini E, Trapani D, et al. Predicting response to antibody drug conjugates: a focus on antigens’ targetability. Oncologist. 2023 Nov;28(11):944–960. doi: 10.1093/ONCOLO/OYAD246
  • Dowell JA, Korth-Bradley J, Liu H, et al. Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in first relapse. J Clin Pharmacol. 2001;41(11):1206–1214. doi: 10.1177/00912700122012751
  • Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov;367(19):1783–1791. doi: 10.1056/NEJMOA1209124/SUPPL_FILE/NEJMOA1209124_DISCLOSURES.PDF
  • Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-college of American pathologists guideline update. J Clin Oncol. 2023 Aug;41(22):3867–3872. doi: 10.1200/JCO.22.02864
  • André F, Hee Park Y, Kim SB, 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 May;401(10390):1773–1785. doi: 10.1016/S0140-6736(23)00725-0
  • Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021 Mar;384(12):1125–1135. doi: 10.1056/NEJMOA2035807
  • Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023 Dec;389(23):2162–2174. doi: 10.1056/NEJMOA2309169
  • Shitara K, Bang Y-J, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020 Jun;382(25):2419–2430. doi: 10.1056/NEJMOA2004413
  • 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 Oct;402(10411):1423–1433. doi: 10.1016/S0140-6736(23)01245-X
  • Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021 Apr;384(16):1529–1541. doi: 10.1056/NEJMOA2028485
  • Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021 Aug;39(22):2474–2485. doi: 10.1200/JCO.20.03489
  • Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022 Jul;387(1):9–20. doi: 10.1056/NEJMOA2203690
  • Li BT, Smit EF, Goto Y, et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med. 2022 Jan;386(3):241–251. doi: 10.1056/NEJMOA2112431
  • Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol. 2024 Jan;42(1):47–58. doi: 10.1200/JCO.23.02005
  • Siena S, Di Bartolomeo M, Raghav K, et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):779–789. doi: 10.1016/S1470-2045(21)00086-3
  • FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors | FDA. [cited 2024 Apr 11]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2
  • Tarantino P, Gupta H, Hughes ME, et al. Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer. Nat Commun. 2023 Dec;14(1). doi: 10.1038/S41467-023-43324-W
  • Mosele F, Deluche E, Lusque A, et al. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nat Med. 2023 Aug;29(8):2110–2120. doi: 10.1038/S41591-023-02478-2
  • Tarantino P, Modi S, Tolaney SM, et al. Interstitial lung disease induced by anti-ERBB2 antibody-drug conjugates: a review. JAMA Oncol. 2021 Dec;7(12):1873–1881. doi: 10.1001/JAMAONCOL.2021.3595
  • Powell CA, Camidge DR, Modi S, et al. 289P risk factors for interstitial lung disease in patients treated with trastuzumab deruxtecan from two interventional studies. Ann Oncol. 2020 Sep;31:S357–S358. doi: 10.1016/J.ANNONC.2020.08.391
  • Izbicki G, Segel MJ, Christensen TG, et al. Time course of bleomycin-induced lung fibrosis. Int J Exp Pathol. 2002;83(3):111–119. doi: 10.1046/J.1365-2613.2002.00220.X
  • Inaba K, Arimoto T, Hoya M, et al. Interstitial pneumonitis induced by pegylated liposomal doxorubicin in a patient with recurrent ovarian cancer. Med Oncol. 2012 Jun;29(2):1255–1257. doi: 10.1007/S12032-011-9893-0
  • Jacobs C, Slade M, Lavery B. Doxorubicin and BOOP. A possible near fatal association. Clin Oncol (R Coll Radiol). 2002;14(3):262. doi: 10.1053/CLON.2002.0071
  • Mazzotta M, Giusti R, Iacono D, et al. Pulmonary fibrosis after pegylated liposomal doxorubicin in elderly patient with cutaneous angiosarcoma. Case Rep Oncol Med. 2016;2016:1–5. doi: 10.1155/2016/8034832
  • Yoshii N, Suzuki T, Nagashima M, et al. Clarification of clinical features of interstitial lung disease induced by irinotecan based on postmarketing surveillance data and spontaneous reports. Anticancer Drugs. 2011 Jul;22(6):563–568. doi: 10.1097/CAD.0B013E3283473F28
  • Willemsen AECAB, Grutters JC, Gerritsen WR, et al. mTOR inhibitor-induced interstitial lung disease in cancer patients: comprehensive review and a practical management algorithm. Int J Cancer. 2016 May;138(10):2312–2321. doi: 10.1002/IJC.29887
  • Shah RR. Tyrosine kinase inhibitor-induced interstitial lung disease: Clinical features, diagnostic challenges, and therapeutic dilemmas. Drug Saf. 2016 Nov;39(11):1073–1091. doi: 10.1007/S40264-016-0450-9
  • Delaunay M, Cadranel J, Lusque A, et al. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. Eur Respir J. 2017 Aug;50(2). doi: 10.1183/13993003.00050-2017
  • Raschi E, Fusaroli M, Ardizzoni A, et al. Cyclin-dependent kinase 4/6 inhibitors and interstitial lung disease in the FDA adverse event reporting system: a pharmacovigilance assessment. Breast Cancer Res Treat. 2021 Feb;186(1):219–227. doi: 10.1007/S10549-020-06001-W
  • Tarantino P, Ricciuti B, Pradhan SM, et al. Optimizing the safety of antibody–drug conjugates for patients with solid tumours. Nat Rev Clin Oncol. 2023 Jun;20(8):558–576. doi: 10.1038/s41571-023-00783-w
  • Baselga J, Albanell J, Molina MA, et al. Mechanism of action of trastuzumab and scientific update. Semin Oncol. 2001 Oct;28(5 Suppl 16):4–11. doi: 10.1016/S0093-7754(01)90276-3
  • 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 Oct;22(20):5097–5108. doi: 10.1158/1078-0432.CCR-15-2822
  • Hunter FW, Barker HR, Lipert B, et al. Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. Br J Cancer. 2019 Dec;122(5):603–612. doi: 10.1038/s41416-019-0635-y
  • Giugliano F, Corti C, Tarantino P, et al. Bystander effect of antibody-drug conjugates: fact or fiction? Curr Oncol Rep. 2022 Jul;24(7):809–817. doi: 10.1007/S11912-022-01266-4
  • Ogitani Y, Hagihara K, Oitate M, et al. 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 Jul;107(7):1039–1046. doi: 10.1111/CAS.12966
  • Li BT, Michelini F, Misale S, et al. Her2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers. Cancer Discov. 2020 May;10(5):674–687. doi: 10.1158/2159-8290.CD-20-0215
  • Doi T, Shitara K, Naito Y, et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody–drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017 Nov;18(11):1512–1522. doi: 10.1016/S1470-2045(17)30604-6
  • 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 Jun;20(6):816–826. doi: 10.1016/S1470-2045(19)30097-X
  • Shitara K, Iwata H, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):827–836. doi: 10.1016/S1470-2045(19)30088-9
  • Tsurutani J, Iwata H, Krop I, et al. Targeting her2 with trastuzumab deruxtecan: a dose-expansion, phase i study in multiple advanced solid tumors. Cancer Discov. 2020 May;10(5):688–701. doi: 10.1158/2159-8290.CD-19-1014
  • 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
  • Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020 Feb;382(7):610–621. doi: 10.1056/NEJMOA1914510
  • Saura C, Modi S, Krop I, et al. Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01). Ann Oncol. 2024 Mar;35(3):302–307. doi: 10.1016/J.ANNONC.2023.12.001
  • Narayan P, Osgood CL, Singh H, et al. FDA approval summary: fam-trastuzumab deruxtecan-nxki for the treatment of unresectable or metastatic HER2-positive breast cancer. Clin Cancer Res. 2021 Aug;27(16):4478–4485. doi: 10.1158/1078-0432.CCR-20-4557
  • Pérez-García JM, Vaz Batista M, Cortez P, et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial. Neuro Oncol. 2023 Jan;25(1):157–166. doi: 10.1093/NEUONC/NOAC144
  • Bartsch R, Berghoff AS, Furtner J, et al. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med. 2022 Sep;28(9):1840–1847. doi: 10.1038/S41591-022-01935-8
  • 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, open-label, phase 3 trial. Lancet. 2023 Jan;401(10371):105–117. doi: 10.1016/S0140-6736(22)02420-5
  • Narayan P, Dilawari A, Osgood C, et al. US food and drug administration approval summary: fam-trastuzumab deruxtecan-nxki for human epidermal growth factor receptor 2-low unresectable or metastatic breast cancer. J Clin Oncol. 2023 Apr;41(11):2108–2116. doi: 10.1200/JCO.22.02447
  • Yamaguchi K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in anti–human epidermal growth factor receptor 2 treatment–naive patients with human epidermal growth factor receptor 2–low gastric or gastroesophageal junction adenocarcinoma: exploratory cohort results in a phase II trial. J Clin Oncol. 2023 Feb;41(4):816. doi: 10.1200/JCO.22.00575
  • Van Cutsem E, di Bartolomeo M, Smyth E, et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. Lancet Oncol. 2023 Jul;24(7):744–756. doi: 10.1016/S1470-2045(23)00215-2
  • Janjigian YY, Oh D-Y, Rha SY, et al. Dose-escalation and dose-expansion study of trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2+ gastric cancer (Gc)/gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03. 2022 Jan;40(4_suppl):295. doi: 10.1200/JCO.2022.40.4_SUPPL.295
  • Shen L, Chen P, Lu J, et al. 172P Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2-positive locally advanced/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): primary efficacy and safety from the phase II single-arm DESTINY-Gastric06 (DG06) trial. Ann Oncol. 2023 Nov;34:S1542–S1543. doi: 10.1016/j.annonc.2023.10.307
  • Goto K, Goto Y, Kubo T, et al. Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 trial. J Clin Oncol. 2023 Nov;41(31):4852–4863. doi: 10.1200/JCO.23.01361
  • FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer | FDA. [cited 2024 Mar 16]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung
  • Raghav KPS, Siena S, Takashima A, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+) metastatic colorectal cancer (mCRC): primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study. 2023 May;41(16_suppl):3501. doi: 10.1200/JCO.2023.41.16_SUPPL.3501
  • Reed DR, Janeway KA, Minard CG, et al. PEPN1924, a phase 2 study of trastuzumab deruxtecan (DS-8201a, T-DXd) in adolescents and young adults with recurrent HER2+ osteosarcoma: a children’s oncology group pediatric early-phase clinical trial network study. 2023 May;41(16_suppl):11527. doi: 10.1200/JCO.2023.41.16_SUPPL.11527
  • Li BT, Meric-Bernstam F, Bardia A, et al. 654O efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with solid tumors harboring specific HER2-activating mutations (HER2m): Primary results from the international phase II DESTINY-PanTumor01 (DPT-01) study. Ann Oncol. 2023 Oct;34:S459–S460. doi: 10.1016/j.annonc.2023.09.1840
  • DiPeri TP, Evans KW, Raso MG, et al. Adavosertib enhances antitumor activity of trastuzumab deruxtecan in HER2-expressing cancers. Clin Cancer Res. 2023 Nov;29(21):OF1–OF14. doi: 10.1158/1078-0432.CCR-23-0103
  • Hamilton EP, Shapiro CL, Boni V, et al. 162O primary analysis from DS8201-A-U105: a 2-part, open label, phase Ib trial assessing trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing advanced breast cancer. Ann Oncol. 2022 May;33:S196. doi: 10.1016/j.annonc.2022.03.181
  • Jhaveri K, André F, Hamilton E, et al. Abstract RF02-03: Trastuzumab deruxtecan (T-DXd) in combination with anastrozole or fulvestrant in patients with HER2-low HR+ advanced/metastatic breast cancer: a phase 1b, open-label, multicenter, dose-expansion study (DESTINY-Breast08). Cancer Res. 2024 May;84(9_Supplement):RF02–03. doi: 10.1158/1538-7445.SABCS23-RF02-03
  • Hurvitz SA, Wang LS, Chan D, 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. 2022 Jun;40(16_suppl):TPS623. doi: 10.1200/JCO.2022.40.16_SUPPL.TPS623
  • Bardia A, Hurvitz S, Press MF, et al. Abstract GS2-03: GS2-03 TRIO-US B-12 TALENT: neoadjuvant trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage breast cancer. Cancer Res. 2023 Mar;83(5_Supplement):GS2–03. doi: 10.1158/1538-7445.SABCS22-GS2-03
  • 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). 2021 May;39(15_suppl):1023. doi: 10.1200/JCO.2021.39.15_SUPPL.1023
  • Schmid P, Wysocki P, Park YH, et al. Abstract PD11-08: PD11-08 Trastuzumab deruxtecan (T-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic hormone receptor-negative (HR−), HER2-low breast cancer: updated results from BEGONIA, a phase 1b/2 study. Cancer Res. 2023 Mar;83(5_Supplement):PD11–08. doi: 10.1158/1538-7445.SABCS22-PD11-08
  • Cheema P, Hartl S, Koczywas M, et al. 695 Efficacy and safety of trastuzumab deruxtecan (T-DXd) with durvalumab in patients with non-small cell lung cancer (HER2 altered NSCLC) who progressed on anti-PD1/PD-L1 therapy (HUDSON). J Immunother Cancer. 2023 Nov;11(Suppl 1):A787–A787. doi: 10.1136/JITC-2023-SITC2023.0695
  • Oliveira C, Mainoli B, Gonçalo SD, et al. Immune-related serious adverse events with immune checkpoint inhibitors: systematic review and network meta-analysis. Eur J Clin Pharmacol. 2024 Feb;80(1):1–10. doi: 10.1007/S00228-024-03647-Z
  • 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 Oct;402(10411):1423–1433. doi: 10.1016/S0140-6736(23)01245-X
  • 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 Feb;42(15):1738–1744. doi: 10.1200/JCO.23.01409
  • Nilsson MB, Poteete A, Udagawa H, et al. Abstract 383: Trastuzumab deruxtecan resistance is associated with reduced responsiveness to topoisomerase inhibitors (payload resistance) but no reduction in sensitivity to HER2 tyrosine kinase inhibitors. Cancer Res. 2023 Apr;83(7_Supplement):383–383. doi: 10.1158/1538-7445.AM2023-383
  • Rolfo C, Del Re M, Russo A. Empower the potential of trastuzumab deruxtecan with novel combinations. Clin Cancer Res. 2023 Nov;29(21):4317–4319. doi: 10.1158/1078-0432.CCR-23-1700