Trastuzumab deruxtecan in patients with locally advanced or metastatic HER2-positive gastric cancer: a multicenter, open-label, expanded-access study.
Expanded-access program
Gastric cancer
Priority review designation system
Trastuzumab deruxtecan
Journal
International journal of clinical oncology
ISSN: 1437-7772
Titre abrégé: Int J Clin Oncol
Pays: Japan
ID NLM: 9616295
Informations de publication
Date de publication:
14 Nov 2023
14 Nov 2023
Historique:
received:
16
05
2023
accepted:
02
10
2023
medline:
15
11
2023
pubmed:
15
11
2023
entrez:
14
11
2023
Statut:
aheadofprint
Résumé
Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that consists of an anti-human epidermal growth factor receptor 2 (HER2) antibody bound by a cleavable tetrapeptide-based linker to a cytotoxic topoisomerase I inhibitor. Prior to marketing approval in Japan in September 2020, this expanded-access study was conducted to provide T-DXd to previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas. This multicenter, open-label, expanded-access study was conducted between March 25 and September 25, 2020 at 17 Japanese sites. Previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas received T-DXd 6.4 mg/kg via intravenous infusions at 3-week intervals. Serious adverse events (SAEs), all potential cases of interstitial lung disease (ILD)/pneumonitis, all liver-related events potentially meeting Hy's Law criteria, and all cases of overdose were reported on the case report forms. A total of 64 patients were treated with T-DXd. Among the 17 (26.6%) patients with reported SAEs, 10 (15.6%) had SAEs related to T-DXd treatment. Febrile neutropenia was the most common SAE (n = 6). SAEs led to death in six patients; drug-related SAEs (sepsis and febrile neutropenia) led to death in one patient. Drug-related ILD, as determined by the external Adjudication Committee, occurred in three patients (Grade 1, Grade 2, and Grade 3: all n = 1). This expanded-access study provided T-DXd to a broader population of Japanese patients prior to marketing approval in Japan, bridging the gap between clinical trials and drug approval. No new safety concerns were identified.
Sections du résumé
BACKGROUND
BACKGROUND
Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that consists of an anti-human epidermal growth factor receptor 2 (HER2) antibody bound by a cleavable tetrapeptide-based linker to a cytotoxic topoisomerase I inhibitor. Prior to marketing approval in Japan in September 2020, this expanded-access study was conducted to provide T-DXd to previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas.
METHODS
METHODS
This multicenter, open-label, expanded-access study was conducted between March 25 and September 25, 2020 at 17 Japanese sites. Previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas received T-DXd 6.4 mg/kg via intravenous infusions at 3-week intervals. Serious adverse events (SAEs), all potential cases of interstitial lung disease (ILD)/pneumonitis, all liver-related events potentially meeting Hy's Law criteria, and all cases of overdose were reported on the case report forms.
RESULTS
RESULTS
A total of 64 patients were treated with T-DXd. Among the 17 (26.6%) patients with reported SAEs, 10 (15.6%) had SAEs related to T-DXd treatment. Febrile neutropenia was the most common SAE (n = 6). SAEs led to death in six patients; drug-related SAEs (sepsis and febrile neutropenia) led to death in one patient. Drug-related ILD, as determined by the external Adjudication Committee, occurred in three patients (Grade 1, Grade 2, and Grade 3: all n = 1).
CONCLUSION
CONCLUSIONS
This expanded-access study provided T-DXd to a broader population of Japanese patients prior to marketing approval in Japan, bridging the gap between clinical trials and drug approval. No new safety concerns were identified.
Identifiants
pubmed: 37964066
doi: 10.1007/s10147-023-02422-x
pii: 10.1007/s10147-023-02422-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s).
Références
Park DI, Yun JW, Park JH et al (2006) HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 51:1371–1379
doi: 10.1007/s10620-005-9057-1
pubmed: 16868827
Kim KC, Koh YW, Chang HM et al (2011) Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol 18:2833–2840
doi: 10.1245/s10434-011-1695-2
pubmed: 21468783
Cho EY, Park K, Do I et al (2013) Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas. Mod Pathol 26:677–684
doi: 10.1038/modpathol.2012.205
pubmed: 23238628
Shan L, Ying J, Lu N (2013) HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagn Pathol 8:76
doi: 10.1186/1746-1596-8-76
pubmed: 23656792
pmcid: 3655831
Yano T, Doi T, Ohtsu A et al (2006) Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep 15:65–71
pubmed: 16328035
Yoon HH, Shi Q, Sukov WR et al (2012) Association of HER2/ErbB2 expression and gene amplification with pathologic features and prognosis in esophageal adenocarcinomas. Clin Cancer Res 18:546–554
doi: 10.1158/1078-0432.CCR-11-2272
pubmed: 22252257
pmcid: 3261584
Yan M, Parker BA, Schwab R et al (2014) HER2 aberrations in cancer: implications for therapy. Cancer Treat Rev 40:770–780
doi: 10.1016/j.ctrv.2014.02.008
pubmed: 24656976
Moasser MM (2007) The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26:6469–6487
doi: 10.1038/sj.onc.1210477
pubmed: 17471238
pmcid: 3021475
Gerson JN, Skariah S, Denlinger CS et al (2017) Perspectives of HER2-targeting in gastric and esophageal cancer. Expert Opin Investig Drugs 26:531–540
doi: 10.1080/13543784.2017.1315406
pubmed: 28387541
pmcid: 5563845
National Comprehensive Cancer Network (2022) NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer version 2.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf . Accessed August 2023.
Lordick F, Carneiro F, Cascinu S et al (2022) Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 33:1005–1020
doi: 10.1016/j.annonc.2022.07.004
pubmed: 35914639
Japanese Gastric Cancer Association (2021) Gastric cancer treatment guidelines for physicians (in Japanese), 6th edn. Kanehara & Co., Ltd, Tokyo
Ogitani Y, Aida T, Hagihara K et al (2016) 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 22:5097–5108
doi: 10.1158/1078-0432.CCR-15-2822
pubmed: 27026201
Ogitani Y, Hagihara K, Oitate M et al (2016) 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 107:1039–1046
doi: 10.1111/cas.12966
pubmed: 27166974
pmcid: 4946713
Daiichi Sankyo Co., Ltd. (2022) Trastuzumab deruxtecan (Enhertu) for intravenous drip infusion [Japanese package insert]. (in Japanese). Available at: https://www.data-index.co.jp/dragdata/pdf/4/430574_4291452D1029_1_07.pdf . Accessed August 2023.
Daiichi Sankyo, Inc. (2022) Trastuzumab deruxtecan (Enhertu [fam-trastuzumab deruxtecan-nxki]) for injection, for intravenous use [US prescribing information]. Available at: https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true . Accessed August 2023.
Daiichi Sankyo Europe GmbH. (2021) Trastuzumab deruxtecan (Enhertu) powder for concentrate for solution for infusion [EU summary of product characteristics]. Available at: https://www.ema.europa.eu/en/documents/product-information/enhertu-epar-product-information_en.pdf . Accessed August 2023.
Shitara K, Bang YJ, Iwasa S et al (2020) Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 382:2419–2430
doi: 10.1056/NEJMoa2004413
pubmed: 32469182
Doi T, Shitara K, Naito Y et al (2017) 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 18:1512–1522
doi: 10.1016/S1470-2045(17)30604-6
pubmed: 29037983
Maeda H, Uchida M, Kusano M et al (2022) Characteristics of the compassionate use program in Japan: an analysis of expanded access clinical trials from 2016 to 2021. Clin Pharmacol Ther 112:817–823
doi: 10.1002/cpt.2641
pubmed: 35569010
pmcid: 9540178
Japan Pharmaceutical Manufacturers Association. Pharmaceutical Administration and Regulations in Japan 2020. Available at: https://www.jpma.or.jp/english/about/parj/eki4g600000078c0-att/2020.pdf . Accessed August 2023.
Japan Ministry of Health and Welfare. (2016) Clinical trials conducted on ethical grounds. Available at: https://www.pmda.go.jp/files/000227843.pdf . Accessed August 2023.
Modi S, Saura C, Yamashita T et al (2019) Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 382:610–621
doi: 10.1056/NEJMoa1914510
pubmed: 31825192
pmcid: 7458671
André F, Hee Park Y, Kim SB et al (2023) 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 401:1773–1785
doi: 10.1016/S0140-6736(23)00725-0
pubmed: 37086745
Cortés J, Kim SB, Chung WP et al (2022) Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med 386:1143–1154
doi: 10.1056/NEJMoa2115022
pubmed: 35320644
Modi S, Jacot W, Yamashita T et al (2022) Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387:9–20
doi: 10.1056/NEJMoa2203690
pubmed: 35665782
pmcid: 10561652
Li BT, Smit EF, Goto Y et al (2022) Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med 386:241–251
doi: 10.1056/NEJMoa2112431
pubmed: 34534430
Yoshino T, Di Bartolomeo M, Raghav K et al (2023) Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 4:3332
doi: 10.1038/s41467-023-38032-4
Yoshihara K, Kobayashi Y, Endo S et al (2023) Trastuzumab deruxtecan dosing in human epidermal growth factor receptor 2-positive gastric cancer: population pharmacokinetic modeling and exposure–response analysis. J Clin Pharmacol (in press). https://doi.org/10.1002/jcph.2295
doi: 10.1002/jcph.2295