Table 2.

Association between HLA-B*57:01 carriage and ALT elevation in pazopanib-treated patients with cancer

	Discovery study					Confirmatory study					Combined analysis
ALT measure	N	Noncarriers, n	Carriers,a n	Effect (95% CI)	P	N	Noncarriers, n	Carriers,a n	Effect (95% CI)	P	N	Noncarriers, n	Carriers, n	Effect (95% CI)	P
MaxALTb	1,188	1,124	64	1.6 (1.3–2.0)	5.0 × 10−5	1,002	935	67	1.2 (0.97–1.51)	0.085	2,190	2,059	131	1.4 (1.2–1.6)	4.3 × 10−5
Time to >3× ULNc	242	219	23	HR = 2.4 (1.5–3.8)	4.8 × 10−4	187	169	18	HR = 3.3 (1.7–6.2)	8.1 × 10−4	429	388	41	HR = 2.5 (1.7–3.6)	5.1 × 10−6
Censored	498	481	17			452	430	22			950	911	39
Time to >5× ULNc	138	121	17	HR = 3.6 (2.1–6.2)	4.1 × 10−5	93	86	7	HR = 4.6 (1.7–12.6)	9.8 × 10−3	231	207	24	HR = 3.4 (2.1–5.5)	5.8 × 10−6
Censored	498	481	17			452	430	22			950	911	39
>3× ULN	242	219	23	OR = 2.3 (1.3–4.1)	0.0039	187	169	18	OR = 1.8 (0.93–3.5)	0.086	429	388	41	OR = 2.0 (1.3–3.1)	0.0014
≤3× ULN	946	905	41			815	766	49			1,761	1,671	90
>5× ULN	138	121	17	OR = 3.1 (1.7–5.8)	7.2 × 10−4	93	86	7	OR = 1.2 (0.45–3.1)	0.75	231	207	24	OR = 2.1 (1.3–3.6)	0.0058
≤5× ULN	1,050	1,003	47			909	849	60			1,959	1,852	107

^aCarriers are patients who carry one or two HL4-B*57:01 alleles. Two and zero patients were HL4-B*57:01 homozygote in the discovery and confirmatory study, respectively. HLA-B*57:01 carriage frequencies were 5%, 7%, and 6% in the discovery, confirmatory, and combined datasets, respectively.

^bRegression was performed using log₁₀ MaxALT; effect was presented as multiplicative (fold-change) effect on MaxALT.

^cPatients with ULN < ALT ≤ 3× ULN were not included in the time-to-event analysis; censored patients had all ALT measures ≤ ULN.