Table 3.

Overview of prospective dose individualization trials of KIs

Drug	n	Patient population	PK parameter	Target	Dose change	PK‐guided dose escalations (↑) or reductions (↓)a	Endpoint	Reference
Everolimus	28	Pediatric SEGA patients	Cmin	5–15 ng/mL	—	↑ and ↓	PD	97
Sunitinib	37	Advanced solid tumors	Cmin	≥50 ng/mL	After 3 and 5 weeks	↑ only	PK	78
Imatinib	56	Chronic myelogenous leukemia patients	Cmin	750–1,500 ng/mL	—	↑ and ↓	PK	25
Pazopanib	13	Renal cell carcinoma patients	AUC	715–920 mg*h/L	After 2 weeks	↑ and ↓	PK	63
Pazopanib	30	Advanced solid tumors	Cmin	≥20 mg/L	After 2, 4, and 6 weeks	↑ only	PK	64

AUC, area under the curve; C_min, minimum plasma concentration/trough concentration; PD, pharmacodynamic; PK, pharmacokinetic; SEGA, subendymal giant cell astrocytoma.

^aPer protocol, some trials had dosing algorithms which allowed for dose reductions (in the absence of toxicity) based on PK, while others only allowed for dose escalation based on PK. All allowed for dose reductions based on toxicity.