Pharmacokinetics of single-agent axitinib across multiple solid tumor types

Area of Science:

• Pharmacology
• Oncology
• Clinical Pharmacokinetics

Background:

• Axitinib, a vascular endothelial growth factor receptor inhibitor, demonstrates antitumor activity.
• Previous trials established axitinib's efficacy as a single agent in several solid tumors.

Purpose of the Study:

• To evaluate and compare the pharmacokinetics of axitinib in patients with non-small cell lung cancer (NSCLC), thyroid cancer, and melanoma.
• To determine if axitinib pharmacokinetics differ across these tumor types.

Main Methods:

• Population pharmacokinetic analysis using nonlinear mixed-effects modeling in 110 patients with NSCLC, thyroid cancer, or melanoma, plus 127 healthy volunteers.
• Comparison of axitinib maximum observed plasma concentration (C max) and area under the plasma concentration-time curve (AUC) against a model developed for metastatic renal cell carcinoma (mRCC).

Main Results:

• A two-compartment model with first-order absorption and lag time best described axitinib disposition.
• Population pharmacokinetic parameters were estimated, with gender and body weight identified as covariates but not clinically meaningful.
• The established pharmacokinetic model for mRCC successfully described axitinib pharmacokinetics in NSCLC, thyroid cancer, and melanoma patients.

Conclusions:

• Axitinib pharmacokinetics are consistent across diverse solid tumor types, including NSCLC, thyroid cancer, and melanoma.
• This pharmacokinetic similarity supports the potential for axitinib as a single-agent therapy across these indications.