Table 3.

Treatment Exposure and Dose Modification Based on Prior Sorafenib/Lenvatinib Treatment (Intent-to-Treat Population)

	Prior sorafenib only		Prior lenvatinib only		Prior lenvatinib and sorafenib
	Cabozantinib n = 63	Placebo n = 33	Cabozantinib n = 68	Placebo n = 34	Cabozantinib n = 39	Placebo n = 21
Duration of exposure, median (range), months	7.0 (0.9–18.8)	3.0 (0.2–15.2)	5.6 (0.2–16.3)	2.5 (0.4–13.8)	5.9 (0.6–16.0)	2.1 (0.8–9.7)
Average daily dose, median (range), mg	41.2 (9.5–60.0)	60.0 (28.3–68.3)	37.4 (10.0–60.0)	58.4 (18.4–60.0)	40.1 (20.2–60.0)	60.0 (34.5–60.0)
Dose modifications due to AE, n (%)	48 (76)	6 (18)	54 (79)	13 (38)	34 (87)	5 (24)
Dose holds due to AE, n (%)	40 (63)	6 (18)	51 (75)	13 (38)	29 (74)	5 (24)
Duration, median (range), months	0.9 (0.1–7.3)	0.6 (0.4–2.1)	1.1 (<0.1–4.7)	0.5 (<0.1–1.2)	0.6 (0.1–2.6)	0.8 (<0.1–2.4)
Dose reduction due to AE, n (%)	45 (71)	1 (3)	42 (62)	2 (6)	27 (69)	0
Reduction to 40 mg	43 (68)	1 (3)	41 (60)	1 (3)	27 (69)	0
Reduction to 20 mg	25 (40)	0	19 (28)	1 (3)	12 (31)	0
Time to first dose level (40 mg) reduction due to AE, median (range), months	2.5 (0.5–16.8)	2.8 (2.8–2.8)	2.0 (0.7–10.2)	3.1 (1.2–5.0)	1.6 (0.5–6.4)	NA
Time to second dose level (20 mg) reduction due to AE, median (range), months	3.7 (0.9–15.5)	NA	4.6 (1.8–12.2)	NA	3.5 (1.0–14.0)	NA
Discontinuation due to a TEAE, n (%)	10 (16)	0	9 (13)	1 (3)	9 (23)	2 (10)
Discontinuation due to a TRAE, n (%)	3 (5)	0	1 (1)	0	6 (15)	0
Grade 5 TEAEs, n (%)	4 (6)	2 (6)	7 (10)	3 (9)	3 (8)	2 (10)
Grade 5 TRAEs, n (%)	0	0	0	0	0	0

AE, adverse event; TEAE; treatment-emergent adverse event; TRAE, treatment-related adverse event.