Table 3.

Exposure–efficacy analyses

Generic name	Cancer	No. of patients	Exposure measure	Dose range	OS	PFS	ORR	irRC	TPR	TSR	BPCTL	References
Ipilimumab	Melanoma	419	Cmin,ss	0.3–10 mg/kg	Positive relationship		Positive relationship	Positive relationship				[15]
			Dose	0.3–10 mg/kg	Positive relationship							[15]
Atezolizumab	Urothelial carcinoma	306	AUC21, AUCss, Cmax, Cmin	1200 mg			No relationship					[18]
	Nonsmall cell lung cancer	653	AUCss	1200 mg			Positive relationship					[19]
Avelumab	Merkel cell carcinoma	88	AUCss, Cave, Cobs-trough,first, Cobs-trough,ss, Ctrough,first, Ctrough,ss	10 mg/kg	AUCss and Ctrough,ss: positive relationship	AUCss and Ctrough,ss: positive relationship	Ctrough,first, AUCss, Cave, Ctrough,ss: positive relationship					[22]
Durvalumab	Urothelial carcinoma	91	Cmax,1, Cmin,2, and Cmin,ss	10 mg/kg			No relationship				No relationship	[29]
Nivolumab	Melanoma	107	Cmin,ss	0.1–10.0 mg/kg			Positive relationship (max. 1 mg/kg)		Inverse relationship (max. 3 mg/kg)	No relationship		[33]
			Dose	0.1–10.0 mg/kg		Numerically higher at 3 mg	No relationship					[33]
		221	Cavg1	0.1–10.0 mg/kg	No relationship		No relationship					[34]
	Nonsmall cell lung cancer	129	Cmin,ss	1–10.0 mg/kg			Positive relationship (max. 3 mg/kg)		No relationship	Positive relationship (max. 3 mg/kg)		[33]
			Dose	1–10.0 mg/kg		Numerically higher at 3 mg	Numerically higher					[33]
	Renal cell carcinoma	34	Cmin,ss	1–10.0 mg/kg			No relationship		No relationship	Positive relationship (max. 3 mg/kg)		[33]
			Dose	1–10.0 mg/kg		Numerically higher at 1 and 10 mg/kg	No relationship					[33]
		Not given	Cavg1, Cavg,ss	0.3–10.0 mg/kg	Cavg,ss: positive relationship							[35]
Pembrolizumab	Melanoma	364/1366	AUCss–6 weeks	2–10.0 mg/kg						No relationship		[43]
	Nonsmall cell lung cancer	496	AUCss–6 weeks	2–10.0 mg/kg			No relationship					[44]

BPCTL best percentage change in target lesion, irRC immune-related response criteria, ORR overall response rate, OS overall survival, PFS progression-free survivalTPR tumor progression rate, TSR tumor shrinkage rate, TSR tumor shrinkage rate, max. maximum, C_trough,ss trough concentration at steady state, C_min,ss minimum concentration at steady state, AUC₂₁ area under the concentration–time curve from time zero to 21 h, AUC_SS area under the concentration–time curve at steady state, C_max maximum concentration, C_min minimum concentration, C_avg average concentration, Cavg,ss average concentration at steady state, C_trough,first trough concentration after the first dose, C_{obs-trough,first} observed trough concentration after the first dose, C_{obs-trough,ss} observed trough concentration at steady-state, C_max,1 maximum plasma concentration after the first dose, C_min,2 minimum plasma concentration after the second dose, C_avg1 time-averaged plasma concentration after the first dose