Evidence map›Paper›PMID 33997928›Full record

ReviewGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021

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

Kohei Shitara, Eishi Baba, Kazumasa Fujitani, Eiji Oki, Satoshi Fujii, Kensei Yamaguchi

Open access · hybridAbstract readReview
In one paragraph

Review in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 4 pooled it
3.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 4 syntheses or guidelines pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study.Journal of clinical pharmacy and therapeutics · 2022
    Pooled it
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  20. Trastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 1 country.

Kohei ShitaraDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. kshitara@east.ncc.go.jp.ORCID 0000-0001-5196-3630
Eishi BabaDepartment of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Kazumasa FujitaniDepartment of Surgery, Osaka Prefectural General Medical Centre, 3-1-56 Bandaihigashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.
Eiji OkiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Satoshi FujiiDepartment of Molecular Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Kensei YamaguchiDepartment of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, Japan.
Kyushu University · JPNational Cancer Center Hospital East · JPOsaka City General Hospital · JPThe Cancer Institute Hospital · JPYokohama City University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

CamptothecinDrug DevelopmentDrug MonitoringDrug-Related Side Effects and Adverse ReactionsErb-b2 Receptor Tyrosine KinasesHumansImmunoconjugatesLung Diseases, InterstitialStomach NeoplasmsTrastuzumabCamptothecinERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmunoconjugatesTrastuzumabtrastuzumab deruxtecanAntibody–drug conjugateGastric cancerHER-2ReviewTopoisomerase I inhibitor

Identifiers

PMID33997928
PMCPMC8205906
OpenAlexW3161258738

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.