. Author manuscript; available in PMC: 2023 Jun 1.

Published in final edited form as: Hepatology. 2022 Apr 7;75(6):1604–1626. doi: 10.1002/hep.32447

Table 7.

Immune-related adverse events reported from clinical trials with ICIs in HCC.

	IMbrave 150 [15] Atezolizumab + Bevacizumab Phase III	CheckMate 040 [68] Nivolumab Phase I/II	CheckMate 040 [80] Nivolumab + Ipilimumab Phase I/II			KEYNOTE 224 [71] Pembrolizumab Phase II	KEYNOTE-240 [72] Pembrolizumab Phase III	NCT02519348 [75] Durvalumab + tremelimumab Phase I/II
No. of patients (intervention arm)	329	48	49	49	48	104	279	74
Dosing	1200 mg atezolizumab + 15 mg/kg bevacizumab q3w	All doses tested in the dose-escalation phase	arm A^†	arm B^††	arm C^†††	200 mg pembrolizumab q3w	200 mg pembrolizumab q3w	T300 + D^*
n (%)
irAEs
any grade	226 (68.7)	N/A	N/A	N/A	N/A	15 (14.4)	51 (18.3)	23 (31.1)
grade ≥3	85 (25.8)	N/A	N/A	N/A	N/A	4 (4)	20 (7.2)	9 (12.2)

irAEs leading to discontinuation of treatment	N/A	N/A	N/A	N/A	N/A	N/A	N/A	9 (12.2)^**

Skin
Rash
any grade	64 (19.5)	15 (31)	17 (35)^a / 0^c	14 (29)^a / 1 (2)^c	8 (17)^a / 0^c	10 (10)^***	32 (11.5)	3 (4.1)
grade ≥3	2 (0.6)	0	3 (6)^a / 0^c	2 (4)^a / 1 (2)^c	0^a / 0^c	0^***	2 (0.7)	1 (1.4)
Pruritus
any grade	43 (13.1)^***	13 (27)	22 (45)^***	16 (33)^***	14 (29)^***	12 (12)^***	51 (18.3)	0
grade ≥3	0^***	0	2 (4)^***	0^***	0^***	0^***	1 (0.4)	0

GI tract
Colitis
any grade	6 (1.8)	N/A	5 (10)^a,b / 2 (4)^b,c	1 (2)^a,b / 0^b,c	1 (2)^a,b / 0^b,c	2 (2)^*****	4 (1.4)^X	3 (4.1)
grade ≥3	2 (0.6)	N/A	3 (6)^a,b / 2 (4)^b,c	1 (2)^a,b / 0^b,c	1 (2)^a,b / 0^b,c	0	2 (0.7)^x	2 (2.7)
Diarrhoea
any grade	34 (10.3)^***	15 (31)				11 (11)^***	48 (17.2)	5 (6.8)
grade ≥3	1 (0.3)^***	1 (2)				0^***	4 (1.4)	0

Liver
Hepatitis
any grade	43 (13.1)^****	2 (4)	10 (20)^a / 3 (6)^c	6 (12)^a / 2 (4)^c	3 (6)^a / 0^c	3 (3)	5 (1.8)	0
grade ≥3	23 (7.0)^****	2 (4)	10 (20)^a / 2 (4)^c	5 (10)^a / 2 (4)^c	3 (6)^a / 0^c	3 (3)	4 (1.4)	0

Endocrine organs
Adrenal insufficency
any grade	1 (0.3)	1 (2)	9 (18)^a / 0^c	3 (6)^a / 0^c	3 (6)^a / 0^c	3 (3)	2 (0.7)	N/A
grade ≥3	0	1 (2)	2 (4)^a / 0^c	0^a / 0^c	0^a / 0^c	2 (2)	0 (0)	N/A
Hypothroidism
any grade	36 (10.9)	2 (4)	10 (20)^a / 0^c	5 (10)^a / 0^c	6 (13)^a / 1 (2)^c	8 (8)	14 (5.0)	4 (5.4)
grade ≥3	0	0	0^a / 0^c	0^a / 0^c	0^a / 0^c	0	1 (0.4)	0
Hyperthyroidism
any grade	15 (4.6)	N/A	5 (10)^a / 0^c	4 (8)^a / 0^c	3 (6)^a / 0^c	1 (1)	9 (3.2)	3 (4.1)
grade ≥3	1 (0.3)	N/A	0^a / 0^c	0^a / 0^c	0^a / 0^c	0	0 (0)	0
Hypophysitis
any grade	N/A	N/A	2 (4)^a / 0^c	1 (2)^a / 0^c	1 (2)^a / 0^c	N/A	2 (0.7)	0
grade ≥3	N/A	N/A	0^a / 0^c	1 (2)^a / 0^c	1 (2)^a / 0^c	N/A	1 (0.4)	0

Lung
Pneumonitis
any grade	4 (1.2)	0	5 (10)^a / 3 (6)^c	0^a / 0^c	0^a / 0^c	N/A	10 (3.6)	1 (1.4)
grade ≥3	0	0	3 (6)^a / 2 (4)^c	0^a / 0^c	0^a / 0^c	N/A	4 (1.4)	1 (1.4)

^†

Arm A: 1 mg/kg nivolumab + 3 mg/kg ipilimumab q3w (4 doses), followed by 240 mg nivolumab q2w.

^††

Arm B: 3 mg/kg nivolumab plus 1 mg/kg ipilimumab q3w (4 doses), followed by 240 mg nivolumab q2w.

^†††

Arm C: 3 mg/kg nivolumab q2w plus 1 mg/kg ipilimumab q6w.

irAEs which required immunosuppressive treattment.

Diarrhoea/colitis combined.

irAEs leading to discontinuation.

T300 + D: 300 mg tremelimuab + 1,500 mg durvalumab (one dose), followed by 1,500 mg duvalumab q4w (this dosing regimen showed the best risk-benefit profile).

^**

Any adverse event resulting in discontinuation of treatment.

^***

Listed as treatment-related adverse event.

^****

Includes only hepatitis (diagnosis), not hepatitis (laboratory abnormality).

^*****

Includes autoimmune colitis and colitis.

Includes colitis, enterocolitis and autoimmune colitis.

N/A: not available, irAEs: immune-related adverse events.