Journal Home > Volume 2 , Issue 5
Cancer Innovation 2023, 2(5): 346-375 https://doi.org/10.1002/cai2.97
Meta-analysis | Open Access | Issue | Published: 15 October 2023

Treatment‐related adverse events of antibody‐drug conjugates in clinical trials: A systematic review and meta‐analysis

Show Author's Information Jinming Li1,2,,  Guoshuang Shen1,2,,  Zhen Liu1,2,,  Yaobang Liu3,  Miaozhou Wang1,2,  Fuxing Zhao1,2,  Dengfeng Ren1,2,  Qiqi Xie1,2,  Zitao Li1,2,  Zhilin Liu1,2,  Yi Zhao1,2,  Fei Ma1,2 ( ),  Xinlan Liu3( ),  Zhengbo Xu4( ),  Jiuda Zhao1,2 ( )
Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai, China
Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer Research, Xining, Qinghai, China
Department of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China
Qinghai University, Xining, Qinghai, China

Jinming Li, Guoshuang Shen, and Zhen Liu contributed equally (co‐first authors).

Keywords:
cancer, clinical trial, adverse event, meta‐analysis, antibody‐drug conjugate
Cite this article:
Li J, Shen G, Liu Z, et al. Treatment‐related adverse events of antibody‐drug conjugates in clinical trials: A systematic review and meta‐analysis. Cancer Innovation, 2023, 2(5): 346-375. https://doi.org/10.1002/cai2.97
Download citation
EndNote(RIS)
BibTeX

273

Views

10

Downloads

Citations

0

Crossref

N/A

WoS

0

Scopus

N/A

CSCD

Abstract Full text About this article
Background

The wide use of antibody‐drug conjugates (ADCs) is transforming the cancer‐treatment landscape. Understanding the treatment‐related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies.

Methods

We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all‐grade and grade ≥ 3 treatment‐related AEs were the primary outcomes of the analysis.

Results

A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any‐grade treatment‐related AEs was 100.0% (95% confidence interval [CI]: 99.9%–100.0%; I2 = 89%) and the incidence of grade ≥ 3 treatment‐related AEs was 6.2% (95% CI: 3.0%–12.4%; I² = 99%).

Conclusions

This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.


menu
Abstract
Full text
Outline
About this article

Treatment‐related adverse events of antibody‐drug conjugates in clinical trials: A systematic review and meta‐analysis

Show Author's information Jinming Li1,2,, Guoshuang Shen1,2,, Zhen Liu1,2,, Yaobang Liu3, Miaozhou Wang1,2, Fuxing Zhao1,2, Dengfeng Ren1,2, Qiqi Xie1,2, Zitao Li1,2, Zhilin Liu1,2, Yi Zhao1,2, Fei Ma1,2 ( ), Xinlan Liu3( ), Zhengbo Xu4( ), Jiuda Zhao1,2 ( )
Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai, China
Qinghai Provincial Clinical Research Center for Cancer; Qinghai Provincial Institute of Cancer Research, Xining, Qinghai, China
Department of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China
Qinghai University, Xining, Qinghai, China

Jinming Li, Guoshuang Shen, and Zhen Liu contributed equally (co‐first authors).

Abstract

Background

The wide use of antibody‐drug conjugates (ADCs) is transforming the cancer‐treatment landscape. Understanding the treatment‐related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies.

Methods

We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all‐grade and grade ≥ 3 treatment‐related AEs were the primary outcomes of the analysis.

Results

A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any‐grade treatment‐related AEs was 100.0% (95% confidence interval [CI]: 99.9%–100.0%; I2 = 89%) and the incidence of grade ≥ 3 treatment‐related AEs was 6.2% (95% CI: 3.0%–12.4%; I² = 99%).

Conclusions

This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.

Keywords: cancer, clinical trial, adverse event, meta‐analysis, antibody‐drug conjugate

References(173)

1

Tarantino P, Carmagnani Pestana R, Corti C, Modi S, Bardia A, Tolaney SM, et al. Antibody‐drug conjugates: smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 2022;72(2):165–182. https://doi.org/10.3322/caac.21705
DOI Google Scholar
2

Chau CH, Steeg PS, Figg WD. Antibody‐drug conjugates for cancer. Lancet. 2019;394(10200):793–804. https://doi.org/10.1016/S0140-6736(19)31774-X
DOI Google Scholar
3

Chia CSB. A patent review on FDA‐approved antibody‐drug conjugates, their linkers and drug payloads. ChemMedChem. 2022;17(11):e202200032. https://doi.org/10.1002/cmdc.202200032
DOI Google Scholar
4

Deeks ED. Disitamab vedotin: first approval. Drugs. 2021;81(16):1929–1935. https://doi.org/10.1007/s40265-021-01614-x
DOI Google Scholar
5

Dhillon S. Moxetumomab pasudotox: first global approval. Drugs. 2018;78(16):1763–1767. https://doi.org/10.1007/s40265-018-1000-9
DOI Google Scholar
6

Gomes‐da‐Silva LC, Kepp O, Kroemer G. Regulatory approval of photoimmunotherapy: photodynamic therapy that induces immunogenic cell death. Oncoimmunology. 2020;9(1):1841393. https://doi.org/10.1080/2162402X.2020.1841393
DOI Google Scholar
7

Professional Committee on Clinical Research of Oncology Drugs, Chinese Anti‐Cancer Association, Expert Committee for Monitoring the Clinical Application of Antitumor Drugs, Breast Cancer Expert Committee of National Cancer Quality Control Center, Cancer Chemotherapy Quality Control Expert Committee of Beijing Cancer Treatment Quality Control and Improvement Center. Expert consensus on the clinical application of antibody‐drug conjugates in the treatment of malignant tumors (2021 edition). Cancer Innovation. 2022;1(1):3–24. https://doi.org/10.1002/cai2.8
DOI Google Scholar
8

Donaghy H. Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody‐drug conjugates. Mabs. 2016;8(4):659–671. https://doi.org/10.1080/19420862.2016.1156829
DOI Google Scholar
9

Wolska‐Washer A, Robak T. Safety and tolerability of antibody‐drug conjugates in cancer. Drug Saf. 2019;42(2):295–314. https://doi.org/10.1007/s40264-018-0775-7
DOI Google Scholar
10

Makawita S, Meric‐Bernstam F. Antibody‐drug conjugates: patient and treatment selection. Am Soc Clin Oncol Educ Book. 2020;40:105–114. https://doi.org/10.1200/EDBK_280775
DOI Google Scholar
11

Conte P, Ascierto PA, Patelli G, Danesi R, Vanzulli A, Sandomenico F, et al. Drug‐induced interstitial lung disease during cancer therapies: expert opinion on diagnosis and treatment. ESMO Open. 2022;7(2):100404. https://doi.org/10.1016/j.esmoop.2022.100404
DOI Google Scholar
12

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097
DOI Google Scholar
13

Zhou X, Yao Z, Bai H, Duan J, Wang Z, Wang X, et al. Treatment‐related adverse events of PD‐1 and PD‐L1 inhibitor‐based combination therapies in clinical trials: a systematic review and meta‐analysis. Lancet Oncol. 2021;22(9):1265–1274. https://doi.org/10.1016/S1470-2045(21)00333-8
DOI Google Scholar
14
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, editors. Cochrane handbook for systematic reviews of interventions. 2nd ed. Chichester (UK): John Wiley & Sons; 2019.
DOI
15

Lin L, Chu H. Meta‐analysis of proportions using generalized linear mixed models. Epidemiology. 2020;31(5):713–717. https://doi.org/10.1097/EDE.0000000000001232
DOI Google Scholar
16

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ. 2003;327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557
DOI Google Scholar
17

Hunter JP, Saratzis A, Sutton AJ, Boucher RH, Sayers RD, Bown MJ. In meta‐analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias. JCE. 2014;67(8):897–903. https://doi.org/10.1016/j.jclinepi.2014.03.003
DOI Google Scholar
18

Egger M, Smith GD, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–634. https://doi.org/10.1136/bmj.315.7109.629
DOI Google Scholar
19

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. https://doi.org/10.1200/JCO.2018.36.15_suppl.1030
DOI Google Scholar
20

Xu Y, Wang Y, Gong J, Zhang X, Peng Z, Sheng X, et al. Phase Ⅰ study of the recombinant humanized anti‐HER2 monoclonal antibody–MMAE conjugate RC48‐ADC in patients with HER2‐positive advanced solid tumors. Gastric Cancer. 2021;24(4):913–925. https://doi.org/10.1007/s10120-021-01168-7
DOI Google Scholar
21

Sheng X, Yan X, Wang L, Shi Y, Yao X, Luo H, et al. Open‐label, multicenter, phase Ⅱ study of RC48‐ADC, a HER2‐targeting antibody‐drug conjugate, in patients with locally advanced or metastatic urothelial carcinoma. Clin Cancer Res. 2021;27(1):43–51. https://doi.org/10.1158/1078-0432.CCR-20-2488
DOI Google Scholar
22

Peng Z, Liu T, Wei J, Wang A, He Y, Yang L, et al. Efficacy and safety of a novel anti‐HER2 therapeutic antibody RC48 in patients with HER2‐overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single‐arm phase Ⅱ study. Cancer Commun. 2021;41(11):1173–1182. https://doi.org/10.1002/cac2.12214
DOI Google Scholar
23

Sheng X, He Z, Shi Y, Luo H, Han W, Yao X, et al. RC48‐ADC for metastatic urothelial carcinoma with HER2‐positive: combined analysis of RC48‐C005 and RC48‐C009 trials. J Clin Oncol. 2022;40(16_suppl):4520. https://doi.org/10.1200/JCO.2022.40.16_suppl.4520
DOI Google Scholar
24

Xu H, Sheng X, Yan X, Chi Z, Cui C, Si L, et al. A phase Ⅱ study of RC48‐ADC in HER2‐negative patients with locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 2020;38(15_suppl):e17113. https://doi.org/10.1200/JCO.2020.38.15_suppl.e17113
DOI Google Scholar
25

Gong J, Shen L, Wang W, Fang J. Safety, pharmacokinetics and efficacy of RC48‐ADC in a phase Ⅰ study in patients with HER2‐overexpression advanced solid cancer. J Clin Oncol. 2018;36(15_suppl):e16059. https://doi.org/10.1200/JCO.2018.36.15_suppl.e16059
DOI Google Scholar
26

Sheng X, He Z, Han W, Zhou AP, Luo H, Shi Y, et al. An open‐label, single‐arm, multicenter, phase Ⅱ study of RC48‐ADC to evaluate the efficacy and safety of subjects with HER2 overexpressing locally advanced or metastatic urothelial cancer (RC48‐C009). J Clin Oncol. 2021;39(15_suppl):4584. https://doi.org/10.1200/JCO.2021.39.15_suppl.4584
DOI Google Scholar
27

Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan in previously treated HER2‐Low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. https://doi.org/10.1056/NEJMoa2203690
DOI Google Scholar
28

Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab deruxtecan in previously treated HER2‐positive gastric cancer. N Engl J Med. 2020;382(25):2419–2430. https://doi.org/10.1056/NEJMoa2004413
DOI Google Scholar
29

Tsurutani J, Iwata H, Krop I, Jänne PA, Doi T, Takahashi S, et al. Targeting HER2 with trastuzumab deruxtecan: a dose‐expansion, phase Ⅰ study in multiple advanced solid tumors. Cancer Discov. 2020;10(5):688–701. https://doi.org/10.1158/2159-8290.CD-19-1014
DOI Google Scholar
30

Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, et al. Trastuzumab deruxtecan in HER2‐mutant non–small‐cell lung cancer. N Engl J Med. 2022;386(3):241–251. https://doi.org/10.1056/NEJMoa2112431
DOI Google Scholar
31

Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, et al. Trastuzumab deruxtecan (DS‐8201a) in patients with advanced HER2‐positive gastric cancer: a dose‐expansion, phase 1 study. Lancet Oncol. 2019;20(6):827–836. https://doi.org/10.1016/S1470-2045(19)30088-9
DOI Google Scholar
32

Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, 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;22(6):779–789. https://doi.org/10.1016/S1470-2045(21)00086-3
DOI Google Scholar
33

Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386(12):1143–1154. https://doi.org/10.1056/NEJMoa2115022
DOI Google Scholar
34

Bartsch R, Berghoff AS, Furtner J, Marhold M, Bergen ES, Roider‐Schur S, et al. Trastuzumab deruxtecan in HER2‐positive breast cancer with brain metastases: a single‐arm, phase 2 trial. Nature Med. 2022;28(9):1840–1847. https://doi.org/10.1038/s41591-022-01935-8
DOI Google Scholar
35

Diéras V, Deluche E, Lusque A, Pistilli B, Bachelot T, Pierga JY, et al. Abstract PD8‐02: trastuzumab deruxtecan (T‐DXd) for advanced breast cancer patients (ABC), regardless HER2 status: a phase Ⅱ study with biomarkers analysis (DAISY. Cancer Res. 2022;82(4_Suppl):PD8‐02. https://doi.org/10.1158/1538-7445.SABCS21-PD8-02
DOI Google Scholar
36

Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, 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. https://doi.org/10.1200/JCO.19.02318
DOI Google Scholar
37

Bando H, Kinoshita I, Modi S, Tsurutani J, Bang YJ, Iwata H, et al. Trastuzumab deruxtecan (T‐DXd) in patients with human epidermal growth factor receptor 2 (HER2)‐expressing salivary duct carcinoma: subgroup analysis of two phase 1 studies. J Clin Oncol. 2021;39(15_suppl):6079. https://doi.org/10.1200/JCO.2021.39.15_suppl.6079
DOI Google Scholar
38

Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, 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. https://doi.org/10.1016/S1470-2045(19)30097-X
DOI Google Scholar
39

Ohba A, Morizane C, Ueno M, Kobayashi S, Kawamoto Y, Komatsu Y, et al. Multicenter phase Ⅱ trial of trastuzumab deruxtecan for HER2‐positive unresectable or recurrent biliary tract cancer: HERB trial. Future Oncol. 2022;18(19):2351–2360. https://doi.org/10.2217/fon-2022-0214
DOI Google Scholar
40

Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, et al. Trastuzumab deruxtecan in previously treated HER2‐positive breast cancer. N Engl J Med. 2020;382(7):610–621. https://doi.org/10.1056/NEJMoa1914510
DOI Google Scholar
41

Yamashita T, Masuda N, Saji S, Araki K, Ito Y, Takano T, et al. Correction to: trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first‐line or second‐line treatment for HER2‐positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non‐inferiority, phase Ⅲ trial in Japan (JBCRG‐M06/EMERALD). Trials. 2020;21(1):503. https://doi.org/10.1186/s13063-020-04408-w
DOI Google Scholar
42

Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, et al. A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2‐positive breast cancer. Cancer. 2012;118(23):5733–5740. https://doi.org/10.1002/cncr.27622
DOI Google Scholar
43

Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, et al. Ado‐trastuzumab emtansine for patients with HER2‐mutant lung cancers: results from a phase Ⅱ basket trial. J Clin Oncol. 2018;36(24):2532–2537. https://doi.org/10.1200/jco.2017.35.15_suppl.8510
DOI Google Scholar
44

Hotta K, Aoe K, Kozuki T, Ohashi K, Ninomiya K, Ichihara E, et al. A phase Ⅱ study of trastuzumab emtansine in HER2‐positive non‐small cell lung cancer. J Thorac Oncol. 2018;13(2):273–279. https://doi.org/10.1016/j.jtho.2017.10.032
DOI Google Scholar
45

Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, et al. Adjuvant trastuzumab emtansine versus paclitaxel in combination with trastuzumab for stage Ⅰ HER2‐positive breast cancer (ATEMPT): a randomized clinical trial. J Clin Oncol. 2021;39(21):2375–2385. https://doi.org/10.1200/JCO.20.03398
DOI Google Scholar
46

Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, et al. Phase Ⅱ randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2‐positive metastatic breast cancer. J Clin Oncol. 2013;31(9):1157–1163. https://doi.org/10.1200/JCO.2012.44.9694
DOI Google Scholar
47

Yamamoto H, Ando M, Aogi K, Iwata H, Tamura K, Yonemori K, et al. Phase Ⅰ and pharmacokinetic study of trastuzumab emtansine in Japanese patients with HER2‐positive metastatic breast cancer. Jpn J Clin Oncol. 2015;45(1):12–18. https://doi.org/10.1093/jjco/hyu160
DOI Google Scholar
48

Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, 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. https://doi.org/10.1200/JCO.2009.26.2071
DOI Google Scholar
49

Burris HA, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, 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. https://doi.org/10.1200/JCO.2010.29.5865
DOI Google Scholar
50

Montemurro F, Ellis P, Anton A, Wuerstlein R, Delaloge S, Bonneterre J, et al. Safety of trastuzumab emtansine (T‐DM1)in patients with HER2‐positive advanced breast cancer: primary results from the KAMILLA study cohort 1. Eur J Cancer. 2019;109:92–102. https://doi.org/10.1016/j.annonc.2020.06.020
DOI Google Scholar
51

Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2‐positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–1791. https://doi.org/10.1056/nejmoa1209124
DOI Google Scholar
52

Peters S, Stahel R, Bubendorf L, Bonomi P, Villegas A, Kowalski DM, et al. Trastuzumab emtansine (T‐DM1) in patients with previously treated HER2‐overexpressing metastatic non‐small cell lung cancer: efficacy, safety, and biomarkers. Clin Cancer Res. 2019;25(1):64–72. https://doi.org/10.1158/1078-0432.ccr-18-1590
DOI Google Scholar
53

Iwama E, Zenke Y, Sugawara S, Daga H, Morise M, Yanagitani N, et al. Trastuzumab emtansine for patients with non‐small cell lung cancer positive for human epidermal growth factor receptor 2 exon‐20 insertion mutations. Eur J Cancer. 2022;162:99–106. https://doi.org/10.1016/j.ejca.2021.11.021
DOI Google Scholar
54

von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2‐positive breast cancer. N Engl J Med. 2019;380(7):617–628. https://doi.org/10.1056/nejmoa1814017
DOI Google Scholar
55

Krop IE, Kim SB, González‐Martín A, LoRusso PM, Ferrero JM, Smitt M, 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. https://doi.org/10.1016/s1470-2045(14)70178-0
DOI Google Scholar
56

Thuss‐Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, et al. Trastuzumab emtansine versus taxane use for previously treated HER2‐positive locally advanced or metastatic gastric or gastro‐oesophageal junction adenocarcinoma (GATSBY): an international randomised, open‐label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18(5):640–653. https://doi.org/10.1016/s1470-2045(17)30111-0
DOI Google Scholar
57

Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2‐positive advanced breast cancer: final results from MARIANNE. Cancer. 2019;125(22):3974–3984. https://doi.org/10.1200/jco.2016.67.4887
DOI Google Scholar
58

Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, et al. Feasibility and cardiac safety of trastuzumab emtansine after anthracycline‐based chemotherapy as (neo)adjuvant therapy for human epidermal growth factor receptor 2‐positive early‐stage breast cancer. J Clin Oncol. 2015;33(10):1136–1142. https://doi.org/10.1200/JCO.2014.58.7782
DOI Google Scholar
59

Brivio E, Locatelli F, Lopez‐Yurda M, Malone A, Díaz‐de‐Heredia C, Bielorai B, et al. A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC‐059 study). Blood. 2021;137(12):1582–1590. https://doi.org/10.1182/blood.2020009407
DOI Google Scholar
60

Goy A, Forero A, Wagner‐Johnston N, Christopher Ehmann W, Tsai M, Hatake K, et al. A phase 2 study of inotuzumab ozogamicin in patients with indolent B‐cell non‐Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy. Br J Haematol. 2016;174(4):571–581. https://doi.org/10.1111/bjh.14094
DOI Google Scholar
61

Pennesi E, Michels N, Brivio E, vander Velden VHJ, Jiang Y, Thano A, et al. Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase Ⅱ trial. Leukemia. 2022;36(6):1516–1524. https://doi.org/10.1038/s41375-022-01576-3
DOI Google Scholar
62

Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, et al. Inotuzumab ozogamicin, an anti‐CD22‐calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012;13(4):403–411. https://doi.org/10.1016/s1470-2045(11)70386-2
DOI Google Scholar
63

Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–753. https://doi.org/10.1056/nejmoa1509277
DOI Google Scholar
64

DeAngelo DJ, Stock W, Stein AS, Shustov A, Liedtke M, Schiffer CA, et al. Inotuzumab ozogamicin in adults with relapsed or refractory CD22‐positive acute lymphoblastic leukemia: a phase 1/2 study. Blood Adv. 2017;1(15):1167–1180. https://doi.org/10.1182/bloodadvances.2016001925
DOI Google Scholar
65

Ogura M, Tobinai K, Hatake K, Uchida T, Kasai M, Oyama T, et al. Phase Ⅰ study of inotuzumab ozogamicin (CMC‐544) in Japanese patients with follicular lymphoma pretreated with rituximab‐based therapy. Cancer Sci. 2010;101(8):1840–1845. https://doi.org/10.1111/j.1349-7006.2010.01601.x
DOI Google Scholar
66

Kantarjian H, Thomas D, Jorgensen J, Kebriaei P, Jabbour E, Rytting M, et al. Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer. 2013;119(15):2728–2736. https://doi.org/10.1002/cncr.28136
DOI Google Scholar
67

Kantarjian HM, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, Gökbuget N, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long‐term survival follow‐up from the randomized, phase 3 INO‐VATE study. Cancer. 2019;125(14):2474–2487. https://doi.org/10.1002/cncr.32116
DOI Google Scholar
68

Kantarjian HM, DeAngelo DJ, Advani AS, Stelljes M, Kebriaei P, Cassaday RD, et al. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open‐label, randomised, phase 3 INO‐VATE study. Lancet Haematology. 2017;4(8):e387–e398. https://doi.org/10.1016/s2352-3026(17)30103-5
DOI Google Scholar
69

DeAngelo DJ, Advani AS, Marks DI, Stelljes M, Liedtke M, Stock W, et al. Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden. Blood Cancer J. 2020;10(8):81. https://doi.org/10.1038/s41408-020-00345-8
DOI Google Scholar
70

de Bono JS, Concin N, Hong DS, Thistlethwaite FC, Machiels JP, Arkenau HT, et al. Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first‐in‐human, multicentre, phase 1–2 trial. Lancet Oncol. 2019;20(3):383–393. https://doi.org/10.1016/s1470-2045(18)30859-3
DOI Google Scholar
71

Hong DS, Concin N, Vergote I, de Bono JS, Slomovitz BM, Drew Y, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer. Clin Cancer Res. 2020;26(6):1220–1228. https://doi.org/10.1158/1078-0432.ccr-19-2962
DOI Google Scholar
72

Coleman RL, Lorusso D, Gennigens C, González‐Martín A, Randall L, Cibula D, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG‐3023/ENGOT‐cx6): a multicentre, open‐label, single‐arm, phase 2 study. Lancet Oncol. 2021;22(5):609–619. https://doi.org/10.1016/s1470-2045(21)00056-5
DOI Google Scholar
73

Yonemori K, Kuboki Y, Hasegawa K, Iwata T, Kato H, Takehara K, et al. Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: results from the innovaTV 206 study. Cancer Sci. 2022;113(8):2788–2797. https://doi.org/10.1111/cas.15443
DOI Google Scholar
74

Hong DS, Birnbaum A, Steuer C, Taylor M, George TJ, Lacy J, et al. Efficacy and safety of tisotumab vedotin in patients with head and neck squamous cell carcinoma: results from a phase Ⅱ cohort. Int J Radiat Oncol*Biol*Phys. 2022;112(5):e10–e11. https://doi.org/10.1016/j.ijrobp.2021.12.028
DOI Google Scholar
75

Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, et al. Sacituzumab govitecan‐hziy in refractory metastatic triple‐negative breast cancer. N Engl J Med. 2019;380(8):741–751. https://doi.org/10.1056/nejmoa1814213
DOI Google Scholar
76

Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, et al. Efficacy and safety of anti‐trop‐2 antibody drug conjugate sacituzumab govitecan (IMMU‐132) in heavily pretreated patients with metastatic triple‐negative breast cancer. J Clin Oncol. 2017;35(19):2141–2148. https://doi.org/10.1200/JCO.2016.70.8297
DOI Google Scholar
77

Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, et al. Sacituzumab govitecan in metastatic triple‐negative breast cancer. N Engl J Med. 2021;384(16):1529–1541. https://doi.org/10.1056/nejmoa2028485
DOI Google Scholar
78

Bardia A, Messersmith WA, Kio EA, Berlin JD, Vahdat L, Masters GA, 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(6):746–756. https://doi.org/10.1016/j.annonc.2021.03.005
DOI Google Scholar
79

Carey LA, Loirat D, Punie K, Bardia A, Diéras V, Dalenc F, et al. Sacituzumab govitecan as second‐line treatment for metastatic triple‐negative breast cancer‐phase 3 ASCENT study subanalysis. NPJ Breast Cancer. 2022;8(1):72. https://doi.org/10.1038/s41523-022-00439-5
DOI Google Scholar
80

O'Shaughnessy J, Brufsky A, Rugo HS, Tolaney SM, Punie K, Sardesai S, et al. Analysis of patients without and with an initial triple‐negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple‐negative breast cancer. Breast Cancer Res Treat. 2022;195(2):127–139. http://doi.org/10.1007/s10549-022-06602-7
DOI Google Scholar
81

Santin A, Komiya T, Goldenberg DM, Sharkey RM, Hong Q, Wegener WA, et al. Sacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase Ⅰ/Ⅱ study. J Clin Oncol. 2020;38(15_suppl):6081. https://doi.org/10.1200/JCO.2020.38.15_suppl.6081
DOI Google Scholar
82

Marmé F, Hanusch C, Furlanetto J, Morris P, Link T, Denkert C, et al. 58O safety interim analysis (SIA) of the phase Ⅲ postneoadjuvant SASCIA study evaluating sacituzumab govitecan (SG) in patients with primary HER2‐negative breast cancer (BC) at high relapse risk after neoadjuvant treatment. Ann Oncol. 2022;33:S148–S149. https://doi.org/10.1016/j.annonc.2022.03.074
DOI Google Scholar
83

Spring L, Tolaney SM, Desai NV, Fell G, Trippa L, Comander AH, et al. Phase 2 study of response‐guided neoadjuvant sacituzumab govitecan (IMMU‐132) in patients with localized triple‐negative breast cancer: results from the NeoSTAR trial. J Clin Oncol. 2022;40(16_suppl):512. https://doi.org/10.1200/JCO.2022.40.16_suppl.512
DOI Google Scholar
84

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O'Shaughnessy J, 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(12):1709–1718. https://doi.org/10.1016/j.annonc.2020.09.004
DOI Google Scholar
85

Tagawa ST, Balar AV, Petrylak DP, Kalebasty AR, Loriot Y, Fléchon A, 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;39(22):2474–2485. https://doi.org/10.1200/JCO.20.03489
DOI Google Scholar
86

Palanca‐Wessels MCA, Czuczman M, Salles G, Assouline S, Sehn LH, Flinn I, et al. Safety and activity of the anti‐CD79B antibody‐drug conjugate polatuzumab vedotin in relapsed or refractory B‐cell non‐hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol. 2015;16(6):704–715. https://doi.org/10.1016/s1470-2045(15)70128-2
DOI Google Scholar
87

Takahashi S, Uemura M, Kimura T, Kawasaki Y, Takamoto A, Yamaguchi A, et al. A phase Ⅰ study of enfortumab vedotin in Japanese patients with locally advanced or metastatic urothelial carcinoma. Invest New Drugs. 2020;38(4):1056–1066. https://doi.org/10.1007/s10637-019-00844-x
DOI Google Scholar
88

Yu EY, Petrylak DP, O'Donnell PH, Lee JL, van der Heijden MS, Loriot Y, et al. Enfortumab vedotin after PD‐1 or PD‐L1 inhibitors in cisplatin‐ineligible patients with advanced urothelial carcinoma (EV‐201): a multicentre, single‐arm, phase 2 trial. Lancet Oncol. 2021;22(6):872–882. https://doi.org/10.1016/s1470-2045(21)00094-2
DOI Google Scholar
89

Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Durán I, Lee JL, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021;384(12):1125–1135. https://doi.org/10.1056/nejmoa2035807
DOI Google Scholar
90

Rosenberg J, Sridhar SS, Zhang J, Smith D, Ruether D, Flaig TW, et al. EV‐101: a phase Ⅰ study of single‐agent enfortumab vedotin in patients with nectin‐4‐positive solid tumors, including metastatic urothelial carcinoma. J Clin Oncol. 2020;38(10):1041–1049. https://doi.org/10.1200/JCO.19.02044
DOI Google Scholar
91

Rosenberg JE, O'Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti‐programmed death 1/programmed death ligand 1 therapy. J Clin Oncol. 2019;37(29):2592–2600. https://doi.org/10.1200/JCO.19.01140
DOI Google Scholar
92

Friedlander TW, Milowsky MI, Bilen MA, Srinivas S, McKay RR, Flaig TW, et al. Study EV‐103: update on durability results and long term outcome of enfortumab vedotin + pembrolizumab in first line locally advanced or metastatic urothelial carcinoma (la/mUC). J Clin Oncol. 2021;39(15_suppl):4528. https://doi.org/10.1200/JCO.2021.39.15_suppl.4528
DOI Google Scholar
93

McGregor BA, Balar AV, Rosenberg JE, Van Der Heijden MS, Park SH, Lee JL, et al. Enfortumab vedotin in cisplatin‐ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD‐1/PD‐L1 inhibitors: an updated analysis of EV‐201 cohort 2. J Clin Oncol. 2021;39(15_suppl):4524. https://doi.org/10.1200/JCO.2021.39.15_suppl.4524
DOI Google Scholar
94

Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, et al. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018;32(8):1768–1777. https://doi.org/10.1038/s41375-018-0210
DOI Google Scholar
95

Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler‐Stevenson M, et al. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long‐term follow‐up. Blood. 2018;131(21):2331–2334. https://doi.org/10.1182/blood-2017-09-803072
DOI Google Scholar
96

Short NJ, Kantarjian H, Jabbour E, Cortes JE, Thomas DA, Rytting ME, et al. A phase Ⅰ study of moxetumomab pasudotox in adults with relapsed or refractory B‐cell acute lymphoblastic leukaemia. Br J Haematol. 2018;182(3):442–444. https://doi.org/10.1111/bjh.14806
DOI Google Scholar
97

Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Robak T, Le Coutre PD, et al. Moxetumomab pasudotox in heavily pre‐treated patients with relapsed/refractory hairy cell leukemia (HCL): long‐term follow‐up from the pivotal trial. J Hematol Oncol. 2021;14(1):35. https://doi.org/10.1186/s13045-020-01004-y
DOI Google Scholar
98

Shah NN, Bhojwani D, August K, Baruchel A, Bertrand Y, Boklan J, et al. Results from an international phase 2 study of the anti‐CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B‐lineage acute lymphoblastic leukemia. Pediatr Blood Cancer. 2020;67(5):e28112. https://doi.org/10.1002/pbc.28112
DOI Google Scholar
99

Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler‐Stevenson M, et al. Phase Ⅰ trial of anti‐CD22 recombinant immunotoxin moxetumomab pasudotox (CAT‐8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012;30(15):1822–1828. https://doi.org/10.1200/JCO.2011.38.1756
DOI Google Scholar
100

Wayne AS, Shah NN, Bhojwani D, Silverman LB, Whitlock JA, Stetler‐Stevenson M, et al. Phase 1 study of the anti‐CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia. Blood. 2017;130(14):1620–1627. https://doi.org/10.1182/blood-2017-02-749101
DOI Google Scholar
101

Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM‐2): a two‐arm, randomised, open‐label, phase 2 study. Lancet Oncol. 2020;21(2):207–221. https://doi.org/10.1016/S1470-2045(19)30788-0
DOI Google Scholar
102

Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. Antibody‐drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase Ⅰ study. Blood Cancer J. 2019;9(4):37. https://doi.org/10.1038/s41408-019-0196-6
DOI Google Scholar
103

Tzogani K, Penttilä K, Lähteenvuo J, Lapveteläinen T, Lopez Anglada L, Prieto C, et al. EMA review of belantamab mafodotin (blenrep) for the treatment of adult patients with relapsed/refractory multiple myeloma. Oncologist. 2021;26(1):70–76. https://doi.org/10.1002/onco.13592
DOI Google Scholar
104

Lonial S, Nooka AK, Thulasi P, Badros AZ, Jeng BH, Callander NS, et al. Management of belantamab mafodotin‐associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM). Blood Cancer J. 2021;11(5):103. https://doi.org/10.1038/s41408-021-00494-4
DOI Google Scholar
105

Richardson PG, Lee HC, Abdallah AO, Cohen AD, Kapoor P, Voorhees PM, et al. Single‐agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM‐2 study. Blood Cancer J. 2020;10(10):106. https://doi.org/10.1038/s41408-020-00369-0
DOI Google Scholar
106

Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. Targeting B‐cell maturation antigen with GSK2857916 antibody‐drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19(12):1641–1653. https://doi.org/10.1016/S1470-2045(18)30576-X
DOI Google Scholar
107

Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B‐cell lymphoma (LOTIS‐2): a multicentre, open‐label, single‐arm, phase 2 trial. Lancet Oncol. 2021;22(6):790–800. https://doi.org/10.1016/S1470-2045(21)00139-X
DOI Google Scholar
108

Jain N, Stock W, Zeidan A, Atallah E, McCloskey J, Heffner L, et al. Loncastuximab tesirine, an anti‐CD19 antibody‐drug conjugate, in relapsed/refractory B‐cell acute lymphoblastic leukemia. Blood Adv. 2020;4(3):449–457. https://doi.org/10.1182/bloodadvances.2019000767
DOI Google Scholar
109

Caimi PF, Ai WZ, Alderuccio JP, Ardeshna KM, Hamadani M, Hess BT, et al. Efficacy and safety of loncastuximab tesirine (ADCT‐402) in relapsed/refractory diffuse large B‐cell lymphoma. Blood. 2020;136:35–37. https://doi.org/10.1182/blood-2020-137524
DOI Google Scholar
110

Kahl BS, Hamadani M, Radford J, Carlo‐Stella C, Caimi P, Reid E, et al. A phase Ⅰ study of ADCT‐402 (loncastuximab tesirine), a novel pyrrolobenzodiazepine‐based antibody‐drug conjugate, in relapsed/refractory B‐cell non‐hodgkin lymphoma. Clin Cancer Res. 2019;25(23):6986–6994. https://doi.org/10.1158/1078-0432.CCR-19-0711
DOI Google Scholar
111

Hamadani M, Radford J, Carlo‐Stella C, Caimi PF, Reid E, O'Connor OA, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B‐cell non‐hodgkin lymphoma. Blood. 2021;137(19):2634–2645. https://doi.org/10.1182/blood.2020007512
DOI Google Scholar
112

Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, et al. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase iii eortc‐gimema aml‐19 trial. J Clin Oncol. 2016;34(9):972–979. https://doi.org/10.1200/JCO.2015.64.0060
DOI Google Scholar
113

Amadori S, Suciu S, Stasi R, Willemze R, Mandelli F, Selleslag D, et al. Gemtuzumab ozogamicin (Mylotarg) as single‐agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: final results of AML‐15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell'Adulto Leukemia Groups. Leukemia. 2005;19(10):1768–1773. https://doi.org/10.1038/sj.leu.2403901
DOI Google Scholar
114

Sievers EL. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33‐positive acute myeloid leukaemia in first relapse. Expert Opin Biol Ther. 2001;1(5):893–901. https://doi.org/10.1517/14712598.1.5.893
DOI Google Scholar
115

Piccaluga PP, Martinelli G, Rondoni M, Malagola M, Gaitani S, Isidori A, et al. Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas. Leuk Lymphoma. 2004;45(9):1791–1795. https://doi.org/10.1080/1042819042000219485
DOI Google Scholar
116

Lo‐Coco F, Cimino G, Breccia M, Noguera NI, Diverio D, Finolezzi E, et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood. 2004;104(7):1995–1999. https://doi.org/10.1182/blood-2004-04-1550
DOI Google Scholar
117

Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33‐positive acute myeloid leukemia in first recurrence. Cancer. 2005;104(7):1442–1452. https://doi.org/10.1002/cncr.21326
DOI Google Scholar
118

Zwaan CM, Reinhardt D, Zimmerman M, Hasle H, Stary J, Stark B, et al. Salvage treatment for children with refractory first or second relapse of acute myeloid leukaemia with gemtuzumab ozogamicin: results of a phase Ⅱ study. Br J Haematol. 2010;148(5):768–776. https://doi.org/10.1111/j.1365-2141.2009.08011.x
DOI Google Scholar
119

Nabhan C, Rundhaugen LM, Riley MB, Rademaker A, Boehlke L, Jatoi M, et al. Phase Ⅱ pilot trial of gemtuzumab ozogamicin (GO) as first line therapy in acute myeloid leukemia patients age 65 or older. Leuk Res. 2005;29(1):53–57. https://doi.org/10.1016/j.leukres.2004.04.011
DOI Google Scholar
120

Arceci RJ, Sande J, Lange B, Shannon K, Franklin J, Hutchinson R, et al. Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia. Blood. 2005;106(4):1183–1188. https://doi.org/10.1182/blood-2004-10-3821
DOI Google Scholar
121

Wang ES, Aplenc R, Chirnomas D, Dugan M, Fazal S, Iyer S, et al. Safety of gemtuzumab ozogamicin as monotherapy or combination therapy in an expanded‐access protocol for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2020;61(8):1965–1973. https://doi.org/10.1080/10428194.2020.1742897
DOI Google Scholar
122

Taksin AL, Legrand O, Raffoux E, De Revel T, Thomas X, Contentin N, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the Alfa group. Leukemia. 2007;21(1):66–71. https://doi.org/10.1038/sj.leu.2404434
DOI Google Scholar
123

Kobayashi Y, Tobinai K, Takeshita A, Naito K, Asai O, Dobashi N, et al. Phase Ⅰ/Ⅱ study of humanized anti‐CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia: final results of Japanese multicenter cooperative study. Int J Hematol. 2009;89(4):460–469. https://doi.org/10.1007/s12185-009-0298-1
DOI Google Scholar
124

Kim YH, Tavallaee M, Sundram U, Salva KA, Wood GS, Li S, et al. Phase Ⅱ investigator‐initiated study of brentuximab vedotin in mycosis fungoides and Sézary syndrome with variable CD30 expression level: a multi‐institution collaborative project. J Clin Oncol. 2015;33(32):3750–3758. https://doi.org/10.1200/JCO.2014.60.3969
DOI Google Scholar
125

Forero‐Torres A, Holkova B, Goldschmidt J, Chen R, Olsen G, Boccia RV, et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015;126(26):2798–2804. https://doi.org/10.1182/blood-2015-06-644336
DOI Google Scholar
126

Ogura M, Tobinai K, Hatake K, Ishizawa K, Uike N, Uchida T, et al. Phase Ⅰ/Ⅱ study of brentuximab vedotin in J apanese patients with relapsed or refractory CD 30‐positive H odgkin's lymphoma or systemic anaplastic large‐cell lymphoma. Cancer Sci. 2014;105(7):840–846. https://doi.org/10.1111/cas.12435
DOI Google Scholar
127

Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, et al. Brentuximab vedotin as consolidation therapy after autologous stem‐cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double‐blind, placebo‐controlled, phase 3 trial. The Lancet. 2015;385(9980):1853–1862. https://doi.org/10.1016/S0140-6736(15)60165-9
DOI Google Scholar
128

Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, et al. Brentuximab vedotin or physician's choice in CD30‐positive cutaneous T‐cell lymphoma (ALCANZA): an international, open‐label, randomised, phase 3, multicentre trial. The Lancet. 2017;390(10094):555–566. https://doi.org/10.1016/S0140-6736(17)31266-7
DOI Google Scholar
129

Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow‐up of the multicohort single‐arm phase Ⅱ CheckMate 205 trial. J Clin Oncol. 2018;36(14):1428–1439. https://doi.org/10.1200/JCO.2017.76.0793
DOI Google Scholar
130

Kuruvilla J, Ramchandren R, Santoro A, Paszkiewicz‐Kozik E, Gasiorowski R, Johnson NA, et al. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE‐204): an interim analysis of a multicentre, randomised, open‐label, phase 3 study. Lancet Oncol. 2021;22(4):512–524. https://doi.org/10.1016/S1470-2045(21)00005-X
DOI Google Scholar
131

Walewski J, Hellmann A, Siritanaratkul N, Ozsan GH, Ozcan M, Chuncharunee S, et al. Prospective study of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi‐agent chemotherapy. Br J Haematol. 2018;183(3):400–410. https://doi.org/10.1111/bjh.15539
DOI Google Scholar
132

Chen R, Palmer JM, Martin P, Tsai N, Kim Y, Chen BT, et al. Results of a multicenter phase Ⅱ trial of brentuximab vedotin as second‐line therapy before autologous transplantation in relapsed/refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2015;21(12):2136–2140. https://doi.org/10.1016/j.bbmt.2015.07.018
DOI Google Scholar
133

Sharman JP, Wheler JJ, Einhorn L, Dowlati A, Shapiro GI, Hilton J, et al. A phase 2, open‐label study of brentuximab vedotin in patients with CD30‐expressing solid tumors. Invest New Drugs. 2019;37(4):738–747. https://doi.org/10.1007/s10637-019-00768-6
DOI Google Scholar
134

Gotlib J, Baird JH, George TI, Langford C, Reyes I, Abuel J, et al. A phase 2 study of brentuximab vedotin in patients with CD30‐positive advanced systemic mastocytosis. Blood Adv. 2019;3(15):2264–2271. https://doi.org/10.1182/bloodadvances.2019000152
DOI Google Scholar
135

Fanale MA, Forero‐Torres A, Rosenblatt JD, Advani RH, Franklin AR, Kennedy DA, et al. A phase Ⅰ weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30‐positive hematologic malignancies. Clin Cancer Res. 2012;18(1):248–255. https://doi.org/10.1158/1078-0432.CCR-11-1425
DOI Google Scholar
136

Kim M, Lee JO, Koh J, Kim TM, Lee JY, Jeon YK, et al. A phase Ⅱ study of brentuximab vedotin in patients with relapsed or refractory Epstein‐Barr virus‐positive and CD30‐positive lymphomas. Haematologica. 2021;106(8):2277–2280. https://doi.org/10.3324/haematol.2021.278301
DOI Google Scholar
137

Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Brentuximab vedotin (SGN‐35) in patients with relapsed or refractory systemic anaplastic large‐cell lymphoma: results of a phase Ⅱ study. J Clin Oncol. 2012;30(18):2190–2196. https://doi.org/10.1200/JCO.2011.38.0402
DOI Google Scholar
138

Song Y, Guo Y, Huang H, Li W, Ke X, Feng J, et al. Phase Ⅱ single‐arm study of brentuximab vedotin in Chinese patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Expert Rev Hematol. 2021;14(9):867–875. https://doi.org/10.1080/17474086.2021.1942831
DOI Google Scholar
139

Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, et al. Brentuximab vedotin (SGN‐35) for relapsed CD30‐positive lymphomas. N Engl J Med. 2010;363(19):1812–1821. https://doi.org/10.1056/NEJMoa1002965
DOI Google Scholar
140

Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, et al. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015;125(9):1394–1402. https://doi.org/10.1182/blood-2014-09-598763
DOI Google Scholar
141

Locatelli F, Mauz‐Koerholz C, Neville K, Llort A, Beishuizen A, Daw S, et al. Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large‐cell lymphoma: a multicentre, open‐label, phase 1/2 study. Lancet Haematol. 2018;5(10):e450–e461. https://doi.org/10.1016/S2352-3026(18)30153-4
DOI Google Scholar
142

Stefoni V, Marangon M, Re A, Lleshi A, Bonfichi M, Pinto A, et al. Brentuximab vedotin in the treatment of elderly Hodgkin lymphoma patients at first relapse or with primary refractory disease: a phase Ⅱ study of FIL ONLUS. Haematologica. 2020;105(10):e512. https://doi.org/10.3324/haematol.2019.243170
DOI Google Scholar
143

Forero‐Torres A, Fanale M, Advani R, Bartlett NL, Rosenblatt JD, Kennedy DA, et al. Brentuximab vedotin in transplant‐naïve patients with relapsed or refractory Hodgkin lymphoma: analysis of two phase Ⅰ studies. Oncologist. 2012;17(8):1073–1080. https://doi.org/10.1634/theoncologist.2012-0133
DOI Google Scholar
144

Zhao B, Chen R, O'Connor OA, Gopal AK, Ramchandren R, Goy A, et al. Brentuximab vedotin, an antibody‐drug conjugate, in patients with CD30‐positive haematologic malignancies and hepatic or renal impairment. Br J Clin Pharmacol. 2016;82(3):696–705. https://doi.org/10.1111/bcp.12988
DOI Google Scholar
145

Gopal AK, Chen R, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015;125(8):1236–1243. https://doi.org/10.1182/blood-2014-08-595801
DOI Google Scholar
146

Kim SJ, Yoon DH, Kim JS, Kang HJ, Lee HW, Eom HS, et al. Efficacy of brentuximab vedotin in relapsed or refractory high‐CD30‐expressing non‐hodgkin lymphomas: results of a multicenter, open‐labeled phase Ⅱ trial. Cancer Res Treat. 2020;52(2):374–387. https://doi.org/10.4143/crt.2019.198
DOI Google Scholar
147

Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Five‐year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562–1566. https://doi.org/10.1182/blood-2016-02-699850
DOI Google Scholar
148

Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E, Holowiecki J, et al. Five‐year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018;132(25):2639–2642. https://doi.org/10.1182/blood-2018-07-861641
DOI Google Scholar
149

Romano A, Parrinello NL, Chiarenza A, Motta G, Tibullo D, Giallongo C, et al. Immune off‐target effects of Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma. Br J Haematol. 2019;185(3):468–479. https://doi.org/10.1111/bjh.15801
DOI Google Scholar
150

DeFilipp Z, Li S, Kempner ME, Brown J, Del Rio C, Valles B, et al. Phase Ⅰ trial of brentuximab vedotin for steroid‐refractory chronic graft‐versus‐host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2018;24(9):1836–1840. https://doi.org/10.1016/j.bbmt.2018.05.012
DOI Google Scholar
151

Duvic M, Tetzlaff M, Clos AL, Gangar P, Talpur R, et al. Phase Ⅱ trial of brentuximab vedotin for CD30+ cutaneous T‐cell lymphomas and lymphoproliferative disorders. Blood. 2013;122(21):367. https://doi.org/10.1182/blood.V122.21.367.367
DOI Google Scholar
152

Ashkar R, Feldman DR, Adra N, Zaid MA, Funt SA, Althouse SK, et al. Phase Ⅱ trial of brentuximab vedotin in relapsed/refractory germ cell tumors. Invest New Drugs. 2021;39(6):1656–1663. https://doi.org/10.1007/s10637-021-01134-1
DOI Google Scholar
153

Horwitz SM, Scarisbrick JJ, Dummer R, Whittaker S, Duvic M, Kim YH, et al. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T‐cell lymphoma: final data. Blood Adv. 2021;5(23):5098–5106. https://doi.org/10.1182/bloodadvances.2021004710
DOI Google Scholar
154

Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Results of a pivotal phase Ⅱ study of Brentuximab Vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012;30(18):2183–2189. https://doi.org/10.1200/JCO.2011.38.0410
DOI Google Scholar
155

Bartlett NL, Chen R, Fanale MA, Brice P, Gopal A, Smith SE, et al. Retreatment with brentuximab vedotin in patients with CD30‐positive hematologic malignancies. J Hematol Oncol. 2014;7:24. https://doi.org/10.1186/1756-8722-7-24
DOI Google Scholar
156

Cognetti DM, Johnson JM, Curry JM, Kochuparambil ST, McDonald D, Mott F, et al. Phase 1/2a, open‐label, multicenter study of RM‐1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma. Head Neck. 2021;43(12):3875–3887. https://doi.org/10.1002/hed.26885
DOI Google Scholar
157

Abuhelwa Z, Alloghbi A, Nagasaka M. A comprehensive review on antibody‐drug conjugates (ADCs) in the treatment landscape of non‐small cell lung cancer (NSCLC. Cancer Treat Rev. 2022;106:102393. https://doi.org/10.1016/j.ctrv.2022.102393
DOI Google Scholar
158

Ungaro A, Tucci M, Audisio A, Di Prima L, Pisano C, Turco F, et al. Antibody‐Drug conjugates in urothelial carcinoma: a new therapeutic opportunity moves from bench to bedside. Cells. 2022;11(5):803. https://doi.org/10.3390/cells11050803
DOI Google Scholar
159

Corti C, Giugliano F, Nicolò E, Ascione L, Curigliano G. Antibody‐drug conjugates for the treatment of breast cancer. Cancers. 2021;13(12):2898. https://doi.org/10.3390/cancers13122898
DOI Google Scholar
160

Perrotti V, Caponio VCA, Mascitti M, Lo Muzio L, Piattelli A, Rubini C, et al. Therapeutic potential of antibody‐drug conjugate‐based therapy in head and neck cancer: a systematic review. Cancers. 2021;13(13):3126. https://doi.org/10.3390/cancers13133126
DOI Google Scholar
161

Masters JC, Nickens DJ, Xuan D, Shazer RL, Amantea M. Clinical toxicity of antibody drug conjugates: a meta‐analysis of payloads. Invest New Drugs. 2018;36(1):121–135. https://doi.org/10.1007/s10637-017-0520-6
DOI Google Scholar
162

Powell CA, Camidge DR, Modi S, Qin A, Taitt C, Lee C, et al. 289P risk factors for interstitial lung disease in patients treated with trastuzumab deruxtecan from two interventional studies. Ann Oncol. 2020;31:S357–S358. https://doi.org/10.1016/j.annonc.2020.08.391
DOI Google Scholar
163

Wahab A, Rafae A, Mushtaq K, Masood A, Ehsan H, Khakwani M, et al. Ocular toxicity of belantamab mafodotin, an oncological perspective of management in relapsed and refractory multiple myeloma. Front Oncol. 2021;11:678634. https://doi.org/10.3389/fonc.2021.678634
DOI Google Scholar
164

Yan H, Endo Y, Shen Y, Rotstein D, Dokmanovic M, Mohan N, et al. Ado‐trastuzumab emtansine targets hepatocytes via human epidermal growth factor receptor 2 to induce hepatotoxicity. Mol Cancer Ther. 2016;15(3):480–490. https://doi.org/10.1158/1535-7163.MCT-15-0580
DOI Google Scholar
165

Endo Y, Takeda K, Mohan N, Shen Y, Jiang J, Rotstein D, et al. Payload of T‐DM1 binds to cell surface cytoskeleton‐associated protein 5 to mediate cytotoxicity of hepatocytes. Oncotarget. 2018;9(98):37200–37215. https://doi.org/10.18632/oncotarget.26461
DOI Google Scholar
166

Swain SM, Nishino M, Lancaster LH, Li BT, Nicholson AG, Bartholmai BJ, et al. Multidisciplinary clinical guidance on trastuzumab deruxtecan (T‐DXd)‐related interstitial lung disease/pneumonitis‐focus on proactive monitoring, diagnosis, and management. Cancer Treat Rev. 2022;106:102378. https://doi.org/10.1016/j.ctrv.2022.102378
DOI Google Scholar
167

Kumagai K, Aida T, Tsuchiya Y, Kishino Y, Kai K, Mori K. Interstitial pneumonitis related to trastuzumab deruxtecan, a human epidermal growth factor receptor 2‐targeting Ab‐drug conjugate, in monkeys. Cancer Sci. 2020;111(12):4636–4645. https://doi.org/10.1111/cas.14686
DOI Google Scholar
168

Powell CA, Modi S, Iwata H, Takahashi S, Smit EF, Siena S, et al. Pooled analysis of drug‐related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open. 2022;7(4):100554. https://doi.org/10.1016/j.esmoop.2022.100554
DOI Google Scholar
169

Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther. 2022;7(1):93. https://doi.org/10.1038/s41392-022-00947-7
DOI Google Scholar
170

Bregni G, Galli G, Gevorgyan A, de Braud F, Di Cosimo S. Trastuzumab cardiac toxicity: a problem we put our heart into. Tumori Journal. 2016;102(1):1–5. https://doi.org/10.5301/tj.5000393
DOI Google Scholar
171

Haddley K. Trastuzumab emtansine for the treatment of HER2‐positive metastatic breast cancer. Drugs Today. 2013;49(11):701–715. https://doi.org/10.1358/dot.2013.49.11.2020937
DOI Google Scholar
172

Tarantino P, Modi S, Tolaney SM, Cortés J, Hamilton EP, Kim SB, et al. Interstitial lung disease induced by anti‐ERBB2 antibody‐drug conjugates: a review. JAMA Oncology. 2021;7(12):1873–1881. https://doi.org/10.1001/jamaoncol.2021.3595
DOI Google Scholar
173

Johns AC, Campbell MT. Toxicities from antibody‐drug conjugates. Cancer J. 2022;28(6):469–478. https://doi.org/10.1097/PPO.0000000000000626
DOI Google Scholar
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 08 July 2023
Accepted: 11 September 2023
Published: 15 October 2023
Issue date: October 2023

Copyright

© 2023 The Authors. Tsinghua University Press.

Acknowledgements

ACKNOWLEDGMENTS

None.

Rights and permissions

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Return