Evidence map›Paper›PMID 33051938›Full record

ArticleCancer science2020

Interstitial pneumonitis related to trastuzumab deruxtecan, a human epidermal growth factor receptor 2-targeting Ab-drug conjugate, in monkeys.

Kazuyoshi Kumagai, Tetsuo Aida, Yoshimi Tsuchiya, Yuki Kishino, Kiyonori Kai, Kazuhiko Mori

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 5 pooled it
5.4field-weighted citation impact, top 3% 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

91 citing papers in PubMed, 5 syntheses or guidelines pooled it, 144 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study.Journal of clinical pharmacy and therapeutics · 2022
    Pooled it
  5. Pooled it
  6. Article
  7. A modular framework for antibody-drug conjugate biomarkers.Nature reviews. Clinical oncology · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

31 more citing papers are in PubMed but not listed here.

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 2 institutions in 2 countries.

Kazuyoshi KumagaiMedicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan.ORCID https://orcid.org/0000-0003-4974-939X
Tetsuo AidaQuantitative Clinical Pharmacology and Translational Sciences, Daiichi Sankyo, Inc, Tokyo, Japan.
Yoshimi TsuchiyaMedicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Yuki KishinoDrug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Kiyonori KaiMedicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Kazuhiko MoriMedicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Daiichi-Sankyo (Japan) · JPDaiichi Sankyo (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Trastuzumab deruxtecan (T-DXd: DS-8201a) is an anti-human epidermal growth factor receptor 2 (HER2) Ab-drug conjugated with deruxtecan (DXd), a derivative of exatecan. The objective of this study was to characterize T-DXd-induced lung toxicity in cynomolgus monkeys. Trastuzumab deruxtecan was injected i.v. into monkeys once every 3 weeks for 6 weeks (10, 30, and 78.8 mg/kg) or for 3 months (3, 10, and 30 mg/kg). To evaluate the involvement of DXd alone in T-DXd-induced toxicity, DXd monohydrate was given i.v. to monkeys once a week for 4 weeks (1, 3, and 12 mg/kg). Interstitial pneumonitis was observed in monkeys given T-DXd at 30 mg/kg or more. The histopathological features of diffuse lymphocytic infiltrates and slight fibrosis were similar to interstitial lung diseases (ILD)/pneumonitis related to anticancer drugs in patients, with an incidence that was dose-dependent and dose-frequency-dependent. Monkeys receiving DXd monohydrate did not suffer lung toxicity, although the DXd exposure level was higher than that of DXd in the monkeys given T-DXd. The HER2 expression in monkey lungs was limited to the bronchial level, although the lesions were found at the alveolar level. Immunohistochemical analysis confirmed that T-DXd localization was mainly in alveolar macrophages, but not pulmonary epithelial cells. These findings indicate that monkeys are an appropriate model for investigating T-DXd-related ILD/pneumonitis. The results are also valuable for hypothesis generation regarding the possible mechanism of T-DXd-induced ILD/pneumonitis in which target-independent uptake of T-DXd into alveolar macrophages could be involved. Further evaluation is necessary to clarify the mechanism of ILD/pneumonitis in patients with T-DXd therapy.

Indexed as

Macaca fascicularisAnimalsCamptothecinCathepsin BDrug Administration ScheduleErb-b2 Receptor Tyrosine KinasesFemaleImmunoconjugatesLungLung Diseases, InterstitialMaleTime FactorsTrastuzumabCamptothecinCathepsin BERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesexatecanImmunoconjugatesTrastuzumabtrastuzumab deruxtecancynomolgus monkeyDS-8201aHER2interstitial lung diseasetrastuzumab deruxtecan

Identifiers

PMID33051938
PMCPMC7734153
OpenAlexW3091949448

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.