Lenvatinib for the treatment of unresectable hepatocellular carcinoma: evidence to date

Figures & data

Table 1 Efficacy results of the REFLECT Phase III trial

Outcome based on investigator assessment per mRECIST	Lenvatinib (n=478)	Sorafenib (n=476)	HR (95% CI)	P-value
Overall response rate	115 (24%)	44 (9.2%)	OR 3.13 (2.15–4.56)	<0.0001
Response
Complete	6 (1%)	2 (<1%)	–	–
Partial	109 (23%)	42 (9%)	–	–
Stable disease	246 (51%)	244 (51%)	–	–
Disease control rate	361 (75.5%)	288 (60.5%)	–	–
Overall survival (months)
Median	13.6	12.3	0.92 (0.79–1.06)	–
95% CI	12.1–14.9	10.4–13.9
Progression-free survival (months)
Median	7.4	3.7	0.66 (0.57–0.77)	<0.0001
95% CI	6.9–8.8	3.6–4.6
Time to progression (months)
Median	8.9	3.7	0.63 (0.53–0.73)	<0.0001
95% CI	(7.4–9.2)	(3.6–5.4)
Outcome based on independent imaging review per mRECIST	Lenvatinib (n=478)	Sorafenib (n=476)	HR (95% CI)	P-value
Overall response rate	194 (40.6%)	59 (12.4%)	OR 5.01 (3.59–7.01)	<0.0001
Response
Complete	10 (2%)	4 (1%)	–	–
Partial	184 (38%)	55 (12%)	–	–
Stable disease	159 (33%)	219 (46%)	–	–
Disease control rate	353 (73.8%)	278 (58.4%)	–	–
Progression-free survival (months)
Median	7.3	3.6	0.64 (0.55–0.75)	<0.0001
95% CI	5.6–7.5	3.6–3.7
Time to progression (months)
Median	7.4	3.7	0.60 (0.51–0.71)	<0.0001
95% CI	(7.2–9.1)	(3.6–3.9)
Outcome based on independent imaging review per RECIST 1.1	Lenvatinib (n=478)	Sorafenib (n=476)	HR (95% CI)	P-value
Overall response rate	90 (18.8%)	31 (6.5%)	OR 3.34 (2.17–5.14)	<0.0001
Response
Complete	2 (<1%)	1 (<1%)	–	–
Partial	88 (18%)	30 (6%)	–	–
Stable disease	258 (54%)	250 (53%)	–	–
Disease control rate	348 (72.8%)	281 (59%)	–	–
Progression-free survival (months)
Median	7.3	3.6	0.65 (0.56–0.77)	<0.0001
95% CI	5.6–7.5	3.6–3.9
Time to progression (months)
Median	7.4	3.7	0.61 (0.51–0.72)	<0.0001
95% CI	(7.3–9.1)	(3.6–5.4)

Abbreviations: mRECIST, modified Response Evaluation Criteria in Solid Tumors; RECIST, Response Evaluation Criteria in Solid Tumors.

Table 2 Most frequent (≥15% of patients) TEAEs in the REFLECT Phase III trial – safety population

Adverse event, n (%)	Lenvatinib (n=476)		Sorafenib (n=475)
	Any grade	Grade ≥3	Any grade	Grade ≥3
Any TEAE	470 (99)	357 (75)	472 (99)	316 (67)
Any treatment-related TEAE	447 (94)	270 (57)	452 (95)	231 (49)
Hypertension	201 (42)	111 (23)	144 (30)	68 (14)
Diarrhea	184 (39)	20 (4)	220 (46)	20 (4)
Decreased appetite	162 (34)	22 (5)	127 (27)	6 (1)
Decreased weight	147 (31)	36 (8)	106 (22)	14 (3)
Fatigue	141 (30)	18 (4)	119 (25)	17 (4)
PPE	128 (27)	14 (3)	249 (52)	54 (11)
Proteinuria	117 (25)	27 (6)	54 (11)	8 (2)
Dysphonia	113 (24)	1 (<1)	57 (12)	0
Nausea	93 (20)	4 (1)	68 (14)	4 (1)
Decreased platelet	87 (18)	26 (5)	58 (12)	16 (3)
Abdominal pain	81 (17)	8 (2)	87 (18)	13 (3)
Vomiting	77 (16)	6 (1)	36 (8)	5 (1)
Constipation	76 (16)	3 (1)	52 (11)	0
Hypothyroidism	78 (16)	0	8 (2)	0
Increased bilirubin	71 (15)	31 (7)	63 (13)	23 (5)
Increased AST	65 (14)	24 (5)	80 (17)	38 (8)
Rash	46 (10)	0	76 (16)	2 (<1)
Alopecia	14 (3)	0	119 (25)	0

Abbreviations: AST, aspartate aminotransferase; PPE, palmar-plantar erythrodysesthesia; TEAE, treatment-emergent adverse event.