A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients

Nivolumab is administered in a weight-based or fixed-flat dosing regimen. For patients with non-small cell lung cancer (NSCLC), a potential exposure-response relationship has recently been reported and may argue against the current dosing strategies. The primary objectives were to determine nivoluma...

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Published in:Journal for immunotherapy of cancer 2019-07, Vol.7 (1), p.192-11, Article 192
Main Authors: Hurkmans, Daan P, Basak, Edwin A, van Dijk, Tanja, Mercieca, Darlene, Schreurs, Marco W J, Wijkhuijs, Annemarie J M, Bins, Sander, Hoop, Esther Oomen-de, Debets, Reno, Joerger, Markus, Odink, Arlette, van der Veldt, Astrid A M, van der Leest, Cor H, Aerts, Joachim G J V, Mathijssen, Ron H J, Koolen, Stijn L W
Format: Article
Language:English
Subjects:
Albumin
Cancer
Cancer metastasis
Cancer research
Cancer therapies
Care and treatment
Cohort analysis
Drug dosages
FDA approval
Immunotherapy
Kidney cancer
Lung cancer
Melanoma
Metastasis
Monoclonal antibodies
Nivolumab
Non-small cell lung cancer
Parameter estimation
Patients
PD-1
Pharmacokinetics
Pharmacology
Small cell lung cancer
Software
Solid tumors
Targeted cancer therapy
Tumors
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Summary:Nivolumab is administered in a weight-based or fixed-flat dosing regimen. For patients with non-small cell lung cancer (NSCLC), a potential exposure-response relationship has recently been reported and may argue against the current dosing strategies. The primary objectives were to determine nivolumab pharmacokinetics (PK) and to assess the relationship between drug clearance and clinical outcome in NSCLC, melanoma, and renal cell cancer (RCC). In this prospective observational cohort study, individual estimates of nivolumab clearance and the impact of baseline covariates were determined using a population-PK model. Clearance was related to best overall response (RECISTv1.1), and stratified by tumor type. Two-hundred-twenty-one patients with metastatic cancer receiving nivolumab-monotherapy were included of whom 1,715 plasma samples were analyzed. Three baseline parameters had a significant effect on drug clearance and were internally validated in the population-PK model: gender, BSA, and serum albumin. Women had 22% lower clearance compared to men, while the threshold of BSA and albumin that led to > 20% increase of clearance was > 2.2m and 
ISSN:2051-1426
2051-1426
DOI:10.1186/s40425-019-0669-y