Table 1. Incidence of adverse events in combination studies with anti-PD-1/anti-PD-L1 agents.

Ref.	Trial	Treatment	Number of patients	AEs (%)	Grade 3/4 AEs (%)	Treatment discontinuation due to AEs (%)
(86)	Phase III	nivo + ipi	945	96%. Diarrhea: 44; Fatigue: 35; Pruritus: 33	58.5%	39.6%
(88)	Phase II	pembro + ipi	153	58%. Diarrhea: 46; Pruritus: 39; Rash: 39	42%	20%
(91)	Phase I	M + T ± D	50	Cohort A (M + T + D): Pyrexia: 63%; Fatigue: 54%	4%	4%
				Cohort B (M + T): Diarrhea: 30%; Rash: 25%
				Cohort C (T→M): Vomiting: 67%
(92)	Phase I/II	pembro + D + T	15	NR	67%	33%
(93)	Phase Ib	A + V + cobi	11	20% (hypertransaminasaemia)	40% elevation of CPK; sepsis; diarrhea and hypertransaminasaemia	9%

anti-PD-1, anti-programmed death antigen-1; anti-PD-L1, anti-programmed death antigen-ligand-1; nivo, nivolumab; ipi, ipilimumab; pembro, pembrolizumab; M, durvalumab; T, trametinib; D, dabrafenib; pts, patients; DLT, dose-limiting toxicity; NR, not reported; A, atezolizumab; V, vemurafenib; cobi, cobimetinib; CPK, creatine-phosphokinase.