Population Pharmacokinetic Analysis of Panitumumab in Patients With Advanced Solid Tumors

  title={Population Pharmacokinetic Analysis of Panitumumab in Patients With Advanced Solid Tumors},
  author={Peiming Ma and Bing‐Bing Yang and Yow-Ming C Wang and Mark C. Peterson and Adimoolam Narayanan and Liviawati Sutjandra and Rachelle Rodriguez and Andrew T. Chow},
  journal={The Journal of Clinical Pharmacology},
Panitumumab is a fully human monoclonal antibody targeted to the extracellular domain of human epidermal growth factor receptor (EGFR). A comprehensive population pharmacokinetic model of panitumumab was developed using nonlinear mixed‐effects modeling of 1200 patients with advanced solid tumors in 14 clinical studies. The disposition of panitumumab was best described with a 2‐compartment model with parallel linear and nonlinear (Michaelis‐Menten) elimination pathways. For a typical male… 

Population pharmacokinetics of farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer

Simulations showed that, when the mg/kg/week dose was maintained, steady-state exposure to farletuzumab was similar with dosing every week or every 3 weeks, and the results support weight-based dosing of farletzumab on a weekly or 3-weekly schedule.

Population pharmacokinetic and covariate analyses of intravenous trastuzumab (Herceptin®), a HER2-targeted monoclonal antibody, in patients with a variety of solid tumors

Trastuzumab PK for the intravenous formulation was well-described across cancer types, disease status, and regimens, and no dose adjustment is required for any of the identified patient covariates.

Differential Pharmacokinetics of Ganitumab in Patients With Metastatic Pancreatic Cancer Versus Other Advanced Solid Cancers

It was found that disease state can significantly affect PK and should be considered when selecting the clinically effective dose of ganitumab, and a two‐compartment model adequately described data over a dose range of 1–20 mg/kg with good predictive capability.

Population pharmacokinetic analysis from phase I and phase II studies of the humanized monovalent antibody, onartuzumab (MetMAb), in patients with advanced solid tumors

Despite the slightly faster clearance, the PK of onartuzumab support dosing regimens of 15 mg/kg every 3 weeks or doses equivalent to achieve the target minimum tumoristatic concentration in patients.

Semimechanistic model to characterize nonlinear pharmacokinetics of nimotuzumab in patients with advanced breast cancer

This model can be very useful for knowing the dosing schedules required for efficacy and supports further investigation of the pharmacokinetic/pharmacodynamic relationships of nimotuzumab to improve its therapeutic use.

Pharmacokinetic and Pharmacodynamic Perspectives on the Clinical Drug Development of Panitumumab

The results of population pharmacokinetic analyses have shown that bodyweight is the most influential covariate on panitumumab exposure, supporting the current use of bodyweight-adjusted doses (mg/kg).

Panitumumab: A Review of Clinical Pharmacokinetic and Pharmacology Properties After Over a Decade of Experience in Patients with Solid Tumors

The pharmacokinetic and pharmacodynamic profile of panitumumab is well suited for standard dosing, and the approved body weight–based dosing regimen maintains efficacy and safety in the treatment of wild-type RAS metastatic colorectal cancer across a broad range of patients.

Population pharmacokinetics of brodalumab in healthy adults and adults with psoriasis from single and multiple dose studies

Body weight (BW) was an important covariate explaining some of the variability in population PK observed in human clinical trials with brodalumab, and based on simulations from the final model, AUC was predicted to be greater than two fold higher in subjects weighing less than 75 kg compared to reference subjects.

Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial

A projected dose and schedule to achieve an empirical target trough concentration (Ctrough) for an anti-fibroblast growth factor receptor 2b antibody, bemarituzumab was projected to achieve 95% receptor occupancy based on in vitro data.

Clinical Pharmacokinetics and Pharmacodynamics of the Epidermal Growth Factor Receptor Inhibitor Panitumumab in the Treatment of Colorectal Cancer

An overview of the clinical pharmacokinetics and pharmacodynamics of panitumumab is presented, including a description of the studies that led to its approval in the different lines of therapy of mCRC.



Population Pharmacokinetics of Cetuximab in Patients With Squamous Cell Carcinoma of the Head and Neck

Clinical dose adjustments beyond the approved body surface area‐based dosing of cetuximab may be warranted in patients with extreme deviations of their actual body weight from ideal body weight.

Clinical pharmacokinetics of bevacizumab in patients with solid tumors

Simulations showed that similar steady-state exposures can be maintained when the weekly mg/kg dose rate is maintained, therefore allowing administration of bevacizumab to coincide with the frequency of administration of the cytotoxic agents.

Dose and Schedule Study of Panitumumab Monotherapy in Patients with Advanced Solid Malignancies

Panitumumab was well tolerated with comparable exposure and safety profiles for the weekly, every 2 weeks, and every 3 weeks administration schedules, most notably in patients with advanced colorectal cancer.

Population pharmacokinetics of trastuzumab in patients With HER2+ metastatic breast cancer

This population pharmacokinetic model can predict trastuzumab exposure in the long-term treatment of patients with metastatic breast cancer and provide comparison of alternative dosage regimens via simulation.

Population Pharmacokinetics of Rituximab (Anti‐CD20 Monoclonal Antibody) in Rheumatoid Arthritis Patients During a Phase II Clinical Trial

No rationale for body surface area‐based dosing for rituximab in rheumatoid arthritis patients was found and the final pharmacokinetic model was used to assess the variability in drug exposure (AUC0‐∞) for fixed versus body surface Area‐ based dosing.

Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer.

  • E. RowinskyG. Schwartz J. Dutcher
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2004
ABX-EGF was generally well tolerated and the objective response rate was low in previously treated patients with metastatic renal cell carcinoma, and its potential as a surrogate marker of clinical benefit requires further evaluation.

Pharmacokinetics and Safety of Golimumab, a Fully Human Anti‐TNF‐α Monoclonal Antibody, in Subjects With Rheumatoid Arthritis

The pharmacokinetics of golimumab appeared to be linear over the dose range evaluated in this study and was generally well tolerated.

Population Pharmacokinetics of Infliximab in Patients With Ankylosing Spondylitis

The development of antibodies to infliximab was associated with accelerated inflixIMab clearance and may represent a potential underlying mechanism for an inadequate response, or loss of response, to inflIXimab treatment.

Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy.

A fully human IgG2kappa monoclonal antibody (MAb), E7.6.3, specific to the human epidermal growth factor (EGF) receptor (EGFr) was generated from human antibody-producing XenoMouse strains engineered

K-ras mutations and benefit from cetuximab in advanced colorectal cancer.

Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ra did benefit fromcetuxIMab.