Evidence map›Paper›PMID 40714515›Full record

Observational studyESMO open2025

Effectiveness of post-trastuzumab deruxtecan treatments and incidence of interstitial lung disease in HER2-positive metastatic breast cancer: a real-world, observational cohort study.

K Nozawa, H Iwata, T Mukohara, T Taira, A Yoshimura, S E Nagai, J Hashimoto, K Matsuura, T Mizuno, Y Shinden and 11 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

21 authors.

K NozawaDepartment of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan; Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. Electronic address: kazuki.nozawa7@gmail.com.
H IwataDepartment of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
T MukoharaDepartment of Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
T TairaDepartment of Oncology, Sagara Hospital, Kagoshima, Japan.
A YoshimuraDepartment of Breast Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
S E NagaiDivision of Breast Oncology, Saitama Cancer Center, Saitama, Japan.
J HashimotoDivision of Medical Oncology, St. Luke's International Hospital, Tokyo, Japan.
K MatsuuraDepartment of Breast Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
T MizunoDepartment of Medical Oncology, Mie University Hospital, Mie, Japan.
Y ShindenDepartment of Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
M YamamotoDepartment of Breast Oncology, Hokkaido Cancer Center, Hokkaido, Japan.
T TakanoDepartment of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
M WakaharaDepartment of Breast and Endocrine Surgery, Tottori University Hospital, Tottori, Japan.
H TerakawaDepartment of Breast Surgery, Kanazawa University Hospital, Ishikawa, Japan.
T YamanakaDepartment of Breast Surgery and Oncology, Kanagawa Cancer Center, Kanagawa, Japan.
Y KojimaInstitute for Clinical Genetics and Genomics, Showa Medical University Hospital, Tokyo, Japan.
T NakayamaDepartment of Breast and Endocrine Surgery, Osaka International Cancer Institute, Osaka, Japan.
Y HirakawaDaiichi Sankyo Co., Ltd., Tokyo, Japan.
K KugeDaiichi Sankyo Co., Ltd., Tokyo, Japan.
A TanabeDaiichi Sankyo Co., Ltd., Tokyo, Japan.
J TsurutaniThe Innovative Center of Translational Research and Clinical Science for Cancer Therapy, Showa Medical University Hospital, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTrastuzumab deruxtecan (T-DXd) is recommended in the second-line or later setting for patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer (mBC). However, clinical evidence for optimal post-T-DXd treatment is lacking. The EN-SEMBLE study examined the distribution of post-T-DXd treatment regimens, their effectiveness, and the incidence of interstitial lung disease (ILD) in the real-world setting. PATIENTS AND

methodsEN-SEMBLE was a real-world, observational, cohort study conducted nationwide in Japan. Patients with HER2-positive mBC who received T-DXd between 25 May 2020 and 30 November 2021 and started another treatment regimen after T-DXd discontinuation were eligible for inclusion. Study outcomes included the distribution of the first post-T-DXd treatments; effectiveness outcomes including real-world progression-free survival (rwPFS) and overall survival (OS); incidence of ILD; and outcomes by patient and treatment characteristics.

resultsThe analysis included 664 patients. The first post-T-DXd treatment was another anti-HER2 therapy in 486/664 patients. This included anti-HER2 antibodies in 361/664 patients, and HER2-tyrosine kinase inhibitors (TKIs) in 113/664 patients. The median first post-T-DXd rwPFS was 4.1 months [95% confidence interval (CI) 3.9-4.5 months], and the median OS was 16.2 months (95% CI 13.8-17.2 months). Outcomes were similar with anti-HER2 antibodies and HER2-TKIs. The rwPFS and OS were numerically longer in patients who discontinued T-DXd due to adverse events (AEs), including ILD, and in patients who had a complete or partial response to T-DXd. The ILD recurrence/exacerbation rate was 3.2% during the first post-T-DXd treatment.

conclusionsSequential HER2-targeted therapy as the first post-T-DXd treatment in HER2-positive mBC was feasible and demonstrated clinical benefit, particularly in patients who discontinued T-DXd treatment due to AEs and those who achieved a response to T-DXd. Patients who developed ILD during T-DXd treatment had a low risk of recurrence/exacerbation in subsequent therapy.

Indexed as

Breast NeoplasmsCamptothecinErb-b2 Receptor Tyrosine KinasesImmunoconjugatesLung Diseases, InterstitialTrastuzumabAdultAgedCohort StudiesFemaleHumansIncidenceJapanMiddle AgedTreatment OutcomeCamptothecinERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmunoconjugatesTrastuzumabtrastuzumab deruxtecaneffectivenesshuman epidermal growth factor receptor 2interstitial lung diseasemetastatic breast cancerpost-trastuzumab deruxtecan treatmentreal-world

Identifiers

PMID40714515
PMCPMC12314378

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Registered trials

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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.