ArticleClinical pharmacology and therapeutics2021
Exposure-Response Relationships in Patients With HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated With Trastuzumab Deruxtecan.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 26 papers, 2 of them syntheses that pooled 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.
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.
Phase 1, Two-Part, Multicenter, Non-randomized, Open-label, Multiple Dose First-In-Human Study of DS-8201A, in Subjects With Advanced Solid Malignant Tumors
A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Postmarketing Assessment of Antibody-Drug Conjugates: Proof-of-Concept Using Model-Based Meta-Analysis and a Clinical Utility Index Approach.CPT: pharmacometrics & systems pharmacology · 2025Pooled it
- Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study.Journal of clinical pharmacy and therapeutics · 2022Pooled it
- Review
- Antibody-Drug Conjugates Targeting HER2 and Trop-2: A New Force in Precision Treatment for Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Clinical Pharmacology and Translational Science Considerations in the Development of Dual-Payload Antibody Drug Conjugates.Clinical and translational science · 2026Review
- Review
- Clinical impact of intratumoral HER2 heterogeneity on trastuzumab deruxtecan efficacy in patients with HER2-positive gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Exposure-Response Relationships of Antibody Drug Conjugates in Solid Tumours.Clinical pharmacokinetics · 2026Review
- Article
- Applications of Pharmacometrics in Antibody-Drug Conjugate Development.Pharmaceutics · 2026Review
- Mapping adverse events and monitoring priorities for trastuzumab deruxtecan use in metastatic breast cancer.International journal of surgery (London, England) · 2026Article
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- Treatment Patterns and Outcomes of Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in Tanzania.JCO global oncology · 2025Article
- Exposure-Response Relationships in Patients with Non-Small-Cell Lung Cancer and Other Solid Tumors Treated with Patritumab Deruxtecan (HER3-DXd).Clinical pharmacology and therapeutics · 2025Article
- Antibody-Drug Conjugates Powered by Deruxtecan: Innovations and Challenges in Oncology.International journal of molecular sciences · 2025Review
- A B7H3-targeting antibody-drug conjugate in advanced solid tumors: a phase 1/1b trial.Nature medicine · 2025Article
- Advances in research and current challenges in the treatment of advanced HER2-low breast cancer.Frontiers in cell and developmental biology · 2025Review
- The efficacy of trastuzumab deruxtecan in Chinese breast cancer patients: a real-world multicenter study.Frontiers in oncology · 2025Article
- Realizing the promise of Project Optimus: Challenges and emerging opportunities for dose optimization in oncology drug development.CPT: pharmacometrics & systems pharmacology · 2024Review
- Impact of using time-averaged exposure metrics on binary endpoints in exposure-response analyses.Frontiers in pharmacology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab deruxtecan (T-DXd) is a HER2-targeting antibody-drug conjugate composed of a novel enzyme-cleavable linker and membrane-permeable topoisomerase I inhibitor payload. T-DXd has been approved for HER2-positive metastatic breast cancer and for HER2-positive metastatic gastric cancer. The approval in breast cancer was based on results from the DESTINY-Breast01 (U201; NCT03248492) and J101 (NCT02564900) trials. Here, we present dose justification for the approved 5.4 mg/kg every-3-weeks (Q3W) dose based on exposure-efficacy evaluated in patients with HER2-positive breast cancer (N = 337) from these 2 trials. Exposure-safety was assessed in patients with all tumor types (N = 639, n = 512 with breast cancer) across 5 trials, including J101 and DESTINY-Breast01. T-DXd doses ranged from 0.8-8.0 mg/kg Q3W; most patients received 5.4 (n = 312) or 6.4 mg/kg (n = 291). For each end point, multivariate logistic or Cox regression analysis was performed using various exposure metrics of T-DXd and released drug. A statistically significant association was observed between intact T-DXd area under the concentration-time curve (AUC) and confirmed objective response rate (ORR; P = 0.028). No significant exposure-response relationships were observed between intact T-DXd or released drug and duration of response or progression-free survival; however, follow-up was limited. All evaluated safety end points demonstrated a significant (P < 0.05) relationship with either intact T-DXd or released drug, with higher adverse event (AE) rates projected at higher exposures. Dose-response projections suggested an increase in ORR (67.5% vs. 62.9%) and toxicity (e.g., grade ≥ 3 all-cause treatment-emergent AEs: 61% vs. 54%) with T-DXd 6.4 vs. 5.4 mg/kg. Results demonstrate the benefit-risk profile at different doses and guide clinicians in the use of the 5.4-mg/kg Q3W dose in patients with HER2-positive metastatic breast cancer.
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What OpenQuestion holds
Registered trials
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.