Trastuzumab deruxtecan for the treatment of patients with HER2-positive gastric cancer

Kotani, Daisuke; Shitara, Kohei

doi:10.1177/1758835920986518

Cited by 22 publications

(19 citation statements)

References 43 publications

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“…The seventh ADC to be approved is Trastuzumab deruxtecan/ Enhertu® (Daiichi Sankyo + AstraZeneca; Figure 7) for the treatment of HER2-positive breast and gastric cancer in 2019. [92][93][94][95][96][97] Its cytotoxin, exatecan/DX-8951 f, is a synthetic derivative of the natural cytotoxin, camptothecin, isolated from the Chinese tree Camptotheca acuminata by Research Triangle Institute researchers in 1966. [98] Exatecan was designed by Daiichi Pharmaceutical Company and Kabushiki Kaisha Yakult Honsha scientists in 1995 (US 5658920, Figure 7).…”

Section: Trastuzumab Deruxtecan/enhertu®mentioning

confidence: 99%

A Patent Review on FDA‐Approved Antibody‐Drug Conjugates, Their Linkers and Drug Payloads

Chia

2022

ChemMedChem

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Antibody‐drug conjugates (ADCs) have emerged as a promising class of biologics since the first approval of Gemtuzumab ozogamicin in 2000. Compared to small molecule drugs, ADCs are structurally much more complex as they comprise of an antibody conjugated to cytotoxic payloads by specially‐designed linkers. Correspondingly, the ADC patent landscape is also much more complex. This review collates and discusses the patents protecting ADCs approved by the FDA up to 31 December 2021, with particular emphasis on their linker and cytotoxin payload technologies.

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Section: Trastuzumab Deruxtecan/enhertu®mentioning

confidence: 99%

A Patent Review on FDA‐Approved Antibody‐Drug Conjugates, Their Linkers and Drug Payloads

Chia

2022

ChemMedChem

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“…Moreover, the phase II/III MAHOGANY trial [49] is currently evaluating margetuximab plus retifanlimab with or without chemotherapy and margetuximab plus tebotelimab with chemotherapy in first-line unresectable metastatic or locally advanced GACs. A combination of T-Dx plus the anti-PD-1 antibody is currently under evaluation in phase I/ II trial NCT04379596 [50].…”

Section: Anti-her2 Targeted Therapymentioning

confidence: 99%

Current molecular biomarkers evaluation in gastric/gastroesophageal junction adenocarcinoma: pathologist does matter

et al. 2022

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The comprehensive molecular characterization of gastric and gastroesophageal junction adenocarcinomas has led to the improvement of targeted and more effective treatments. As a result, several biomarkers have been introduced into clinical practice and the implementation of innovative diagnostic tools is under study. Such assessments are mainly based on the evaluation of limited biopsy material in clinical practice. In this setting, the pathologist represents a key player in the selection of patients facilitating precision medicine approaches.

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“…The median duration of confirmed objective response for T-DXd was 11.3 months, which was notable considering that the duration of response for first-line trastuzumab plus chemotherapy treatment was reported as 6.9 months [ 9 ]. These well-known trials are reviewed in a recent publication by Kotani and Shitara [ 32 ].…”

Section: Therapeutic Efficacymentioning

confidence: 99%

Discovery and development of trastuzumab deruxtecan and safety management for patients with HER2-positive gastric cancer

Shitara

Baba

Fujitani³

et al. 2021

Gastric Cancer

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Approximately 12–15% of gastric cancers (GCs) are human epidermal growth factor receptor-2 (HER2)-positive (HER2 immunohistochemistry 3 + or 2 + /in situ hybridization + [ERBB2/CEP17 ≥ 2.0]). While the anti-HER2 monoclonal antibody trastuzumab, in combination with chemotherapy, is the standard treatment for HER2-positive GC, other HER2-targeted therapies have not demonstrated survival benefits in patients with GC, despite showing efficacy in patients with HER2-positive breast cancer. This indicates that there are unique challenges to the use of currently available HER2-targeted therapies for the treatment of HER2-positive GC. Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate consisting of an anti-HER2 human monoclonal IgG1 antibody with the same amino acid sequence as trastuzumab, an enzymatically cleavable peptide-based linker, and DXd, a novel topoisomerase I inhibitor, as its released payload. T-DXd has a high drug–antibody ratio (approximately 8) and a demonstrated bystander antitumor effect. It has demonstrated significant efficacy when compared with standard therapies and is approved as third- or later-line treatment for HER2-positive GC in Japan and second- or later-line treatment in the US. T-DXd treatment is associated with gastrointestinal and hematological adverse events, and a risk of interstitial lung disease (ILD), with the ILD risk being higher in Japan than in countries other than Japan. However, most adverse events, including ILD, can be managed with proactive monitoring and T-DXd dose modification, and initiation of adequate treatment. In this review, we summarize the discovery and development of T-DXd and provide guidance for T-DXd safety management, including ILD monitoring, for patients with HER2-positive GC.

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Trastuzumab deruxtecan for the treatment of patients with HER2-positive gastric cancer

Cited by 22 publications

References 43 publications

A Patent Review on FDA‐Approved Antibody‐Drug Conjugates, Their Linkers and Drug Payloads

A Patent Review on FDA‐Approved Antibody‐Drug Conjugates, Their Linkers and Drug Payloads

Current molecular biomarkers evaluation in gastric/gastroesophageal junction adenocarcinoma: pathologist does matter

Discovery and development of trastuzumab deruxtecan and safety management for patients with HER2-positive gastric cancer

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