Evaluating the impact of relative dose intensity on efficacy of trastuzumab deruxtecan for metastatic breast cancer in the real-world clinical setting.
10.47102/annals-acadmedsg.202576
- Author:
Han Yi LEE
1
;
Vivianne SHIH
2
;
Jack Junjie CHAN
1
;
Shun Zi LIONG
3
;
Ryan Shea Ying Cong TAN
1
;
Jun MA
1
;
Bernard Ji Guang CHUA
1
;
Joshua Zhi Chien TAN
1
;
Chuan Yaw LEE
1
;
Wei Ling TEO
2
;
Su-Ming TAN
4
;
Phyu NITAR
4
;
Yoon Sim YAP
1
;
Mabel WONG
1
;
Rebecca DENT
1
;
Fuh Yong WONG
5
;
Tira J TAN
1
Author Information
1. Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
2. Department of Pharmacy, National Cancer Centre Singapore, Singapore.
3. Division of Clinical Trials & Epidemiology Sciences, National Cancer Centre Singapore, Singapore.
4. Breast Surgery, Changi General Hospital, Singapore.
5. Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.
- Publication Type:Journal Article
- Keywords:
cancer;
internal medicine;
oncology;
pharmacology;
public health
- MeSH:
Humans;
Female;
Breast Neoplasms/mortality*;
Middle Aged;
Trastuzumab/adverse effects*;
Aged;
Adult;
Singapore/epidemiology*;
Antineoplastic Agents, Immunological/adverse effects*;
Camptothecin/adverse effects*;
Immunoconjugates/adverse effects*;
Retrospective Studies;
Progression-Free Survival;
Receptor, ErbB-2/metabolism*;
Neoplasm Metastasis;
Dose-Response Relationship, Drug;
Treatment Outcome;
Registries
- From:Annals of the Academy of Medicine, Singapore
2025;54(8):458-466
- CountrySingapore
- Language:English
-
Abstract:
INTRODUCTION:Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges.
METHOD:Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes.
RESULTS:Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities.
CONCLUSION:Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
