. 2021 Dec 1;6(6):100312. doi: 10.1016/j.esmoop.2021.100312

Table 2.

Exposure-toxicity and exposure-efficacy relationship in anti-vascular endothelial growth factor receptor 2 tyrosine kinase inhibitors in metastatic renal cell carcinoma

Drug	PK parameter	Safety	Efficacy
Axitinib¹⁶^,¹⁷	AUC at 4 weeks from treatment start	—	• >300 ng h/ml: better OS and PFS • 154-620 ng h/ml better OS and PFS
Axitinib¹⁶^,¹⁷	C_ss,trough	• >6.6 ng/ml associated with ≥G2 hypothyroidism. • >7.1 ng/ml associated with ≥G2 asthenia	• >5 ng/ml associated with longer OS
Pazopanib¹⁸^,¹⁹	C_ss,trough	• ≥15 μg/ml associated with higher rate of hypertension	• ≥15 μg/ml associated with PR/SD • <15 μg/ml associated with PD • ≥20.5 μg/ml longer PFS and greater tumor shrinkage
Sunitinib20, 21, 22, 23	C_ss,trough	• ≥100 ng/ml higher toxicity rate	• Optimal concentration between 50 and 100 ng/ml (preclinical data) • <100 ng/ml associated with longer PFS and TTF • >100 ng/ml associated with worse outcomes
Sunitinib20, 21, 22, 23	AUC_ss	• >2150 ng/ml/h higher grade 3-4 toxicity	• Lower in PD patients compared with AUC_ss at treatment start.

AUC, area under the curve; AUC_ss, AUC at steady state; C_ss,trough, residual concentration at steady state; OS, overall survival; PD, pharmacodynamics; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response; SD, stable disease; TTF, time to treatment failure.