Table 1.

Key details of recent breakthrough studies in metastatic melanoma.

	BRIM-3 [Chapman et al. 2011]	BREAK-3 [Hauschild et al. 2012]	METRIC [Flaherty et al. 2012b]	COMBI- v [Robert et al. 2014]	MEK162 [Ascierto et al. 2013]	Imatinib [Guo et al. 2011]	Ipilimumab [Hodi et al. 2010]	Ipilimumab/ dacarbazine [Robert et al. 2011]	Nivolumab [Topalian et al. 2014]
Phase	III	III	III	III	II	II	III	III	I/II
Line of treatment	1st	1stt	1st or 2nd	1st	>2nd	2ndor 3nd	2nd	1nd	> 2nd
Number of patients	675	250	322	704	71	43	676	502	107
Drug	Vemurafenib	Dabrafenib	Trametinib	Dabrafenib/ trametinib	MEK162	Imatinib	Ipilimumab	Ipilimumab/ dacarbazine	Nivolumab
Mechanism	BrafV600 inhibitor	BrafV600 inhibitor	MEK inhibitor	BrafV600 inhibitor + MEK inhibitor	MEK inhibitor	KIT inhibitor	Anti-CTLA-4 antibody	Anti-CTLA-4 antibody + cytotoxic	Anti-PD-1 antibody
Patient selection	BrafV600E or V600K mutated	BrafV600 mutated	BrafV600 mutated	BrafV600 mutated	BrafV600 or NRAS-mutated	cKIT mutated and/or amplified	HLA-A*0201 positive	no	no
RR (%)	57	50	22	N/A	20*	22	10.9	15	31¥
Median PFS (months)	6.9*	6.9*	4.8*	11.4	4	3.5*	2.9	<3	3.7
Median OS (months)	13.6	18.2	Not mature	Not mature*	Not mature	Not mature	10.1*	11.2*	16.8

All trials were considered to have positive results. Last three columns detail clinical trials with immune checkpoint antibodies.

^*Primary endpoint

^¥Secondary endpoint

MEK, mitogen-activated protein kinase kinase; OS, overall survival; PFS, progression-free survival; RR, relative risk.