The impact of hepatic and renal function on panitumumab exposures in patients with metastatic RAS wild-type colorectal cancer

Autor: Hans Prenen, Sandeep Dutta, Vijay V. Upreti, Michael Z Liao
Rok vydání: 2021
Předmět:
Male
Cancer Research
Dose adjustment
Colorectal cancer
Toxicology
Severity of Illness Index
030226 pharmacology & pharmacy
Gastroenterology
Antineoplastic Agents
Immunological
0302 clinical medicine
Pharmacology (medical)
Epidermal growth factor receptor
Renal impairment
RAS wild-type
Randomized Controlled Trials as Topic
education.field_of_study
biology
Panitumumab
Liver Diseases
Pharmacology. Therapy
Middle Aged
Hepatic impairment
Oncology
030220 oncology & carcinogenesis
Original Article
Administration
Intravenous
Female
Kidney Diseases
medicine.symptom
Colorectal Neoplasms
medicine.drug
medicine.medical_specialty
Population
Cmax
Renal function
03 medical and health sciences
Clinical Trials
Phase II as Topic
Pharmacokinetics
Internal medicine
medicine
Humans
education
Aged
Pharmacology
business.industry
Organ dysfunction
medicine.disease
Clinical Trials
Phase III as Topic
ras Proteins
biology.protein
Human medicine
business
Zdroj: Cancer chemotherapy and pharmacology
Cancer Chemotherapy and Pharmacology
ISSN: 1432-0843
0344-5704
DOI: 10.1007/s00280-021-04319-w
Popis: Purpose Panitumumab is a human monoclonal antibody targeting the epidermal growth factor receptor for the treatment of wild-type RAS metastatic colorectal cancer (mCRC). Currently, no dedicated clinical studies have evaluated the effect of organ impairment on the pharmacokinetics of panitumumab. Here, we present data from late phase studies of panitumumab in patients with mCRC and analyses of the effect of hepatic or renal impairment on the exposure of panitumumab. Methods From three multicenter, open-label, phase 2 and phase 3 studies, 349 and 351 patients were included in hepatic and renal function subgroup analyses, respectively. Patients who received IV panitumumab and serum exposures were compared to patients with varying degrees of hepatic and renal organ dysfunction. Results The Cmax and Ctrough values for patients with mild (n = 119) and moderate (n = 4) hepatic impairment were within the range of serum concentrations of panitumumab for the normal hepatic function subgroup. The distributions of serum concentration of panitumumab in patients with mild (n = 85) or moderate (n = 19) renal impairment were similar to the serum concentrations of panitumumab in the normal renal function subgroup. Population pharmacokinetic modeling and covariate analysis results were also consistent with lack of any significant effect of renal or hepatic impairment on the pharmacokinetics of panitumumab. Additionally, real-world evidence from case studies of patients with mCRC and severe hepatic or renal impairment, which is a rare patient population to study, indicated lack of clinically relevant differences in exposure of panitumumab compared with patients with mCRC and normal hepatic or renal function. Conclusions Mild-to-moderate hepatic or renal dysfunction had no clinically meaningful impact on the pharmacokinetics of panitumumab in patients with mCRC. No dose adjustments for panitumumab are warranted in patients with mCRC with mild-to-moderate hepatic or renal dysfunction. Trial registration ClinicalTrials.gov; NCT00083616, NCT00089635, NCT00113763
Databáze: OpenAIRE
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