ArticleCancer chemotherapy and pharmacology2014
Population pharmacokinetics of trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer: clinical implications of the effect of covariates.
Article in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- Research hotspots and trends in therapeutic drug monitoring of anticancer drugs: a 1990-2024 bibliometric analysis.Frontiers in oncology · 2026Pooled it
- 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
- Covariate analysis of tusamitamab ravtansine, a DM4 anti-CEACAM5 antibody-drug conjugate, based on first-in-human study.CPT: pharmacometrics & systems pharmacology · 2022Trial
- Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer.Cancer chemotherapy and pharmacology · 2019Trial
- A Pharmacometric Analysis of Patient-Reported Outcomes in Breast Cancer Patients Through Item Response Theory.Pharmaceutical research · 2018Trial
- Population pharmacokinetics and exposure-response of trastuzumab emtansine in advanced breast cancer previously treated with ≥2 HER2-targeted regimens.British journal of clinical pharmacology · 2017Trial
- From Payload-First Toward Dual-Mechanism Antibody-Drug Conjugates.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Human Pharmacokinetic Prediction of Antibody-Drug Conjugates Using Human FcRn Transgenic Mice.Clinical and translational science · 2026Article
- Exposure-Response Relationships of Antibody Drug Conjugates in Solid Tumours.Clinical pharmacokinetics · 2026Review
- Optimizing Body Size-Based Dosing Approaches for Antibody-Drug Conjugates.Clinical pharmacology and therapeutics · 2026Review
- Applications of Pharmacometrics in Antibody-Drug Conjugate Development.Pharmaceutics · 2026Review
- Review
- [Advances in Antibody-drug Conjugates for Non-small Cell Lung Cancer after Resistance to First-line Therapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- T-DM1 with concurrent radiotherapy in HER2-positive breast cancer: preclinical evaluation and mechanisms, prediction, and exploration of adverse effects.Discover oncology · 2025Review
- Antibody-drug conjugates in elderly patients with breast cancer.Breast (Edinburgh, Scotland) · 2025Review
- Efficacy of innovative systemic treatments in combination with radiotherapy for bone metastases: a GEMO (the European Study Group of Bone Metastases) state of the art.Cancer metastasis reviews · 2025Review
- Obesity, overweight and breast cancer: new clinical data and implications for practice.Frontiers in oncology · 2025Review
- Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases.NPJ breast cancer · 2024Article
- A Sequential Population Pharmacokinetic Model of Zilovertamab Vedotin in Patients with Hematologic Malignancies Extrapolated to the Pediatric Population.Clinical pharmacokinetics · 2024Article
- Systemic oncological therapy in breast cancer patients on dialysis.World journal of clinical oncology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTrastuzumab emtansine (T-DM1) is an antibody-drug conjugate comprising the humanized monoclonal antibody trastuzumab linked to DM1, a highly potent cytotoxic agent. A population pharmacokinetic (PK) analysis was performed to estimate typical values and interindividual variability of T-DM1 PK parameters and the effects of clinically relevant covariates.
methodsSerum samples were collected from 671 patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer (MBC) who received single-agent T-DM1 in five phase I to phase III studies. Nonlinear mixed-effects modeling with the first-order conditional estimation method was used.
resultsA linear two-compartment model with first-order elimination from the central compartment described T-DM1 PKs in the clinical dose range. T-DM1 elimination clearance was 0.676 L/day, volume of distribution in the central compartment (V c) was 3.127 L, and terminal elimination half-life was 3.94 days. Age, race, region, and renal function did not influence T-DM1 PK. Given the low-to-moderate effect of all statistically significant covariates on T-DM1 exposure, none of these covariates is expected to result in a clinically meaningful change in T-DM1 exposure.
conclusionsT-DM1 PK properties are consistent and predictable in patients. A further refinement of dose based on baseline covariates other than body weight for the current 3.6 mg/kg regimen would not yield clinically meaningful reductions in interindividual PK variability in patients with MBC.
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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.