Table 2. Phase III trials of targeted therapy in metastatic melanoma with a BRAF mutation.

Study (publication)	Treatment arm	Tumor stages	Number of patients	Median follow-up	Response rates	Median progression free survival	Median overall survival	Patients with raised LDH at the time of inclusion in the study	Proportions of M1c
COMBI-d (21)	Dabrafenib 150 mg BID/trametinib 2 mg/d	IIIC-IV BRAF-V600 mutation	211	36 months	68%	11.0 months	25.1 months	36%	67%
	Dabrafenib 150 mg BID/placebo		212		55%	8.8 months	18.7 months	33%	65%
COMBI-v (22)	Dabrafenib 150 mg BID/trametinib 2 mg/d	IIIC-IV BRAF-V600 mutation	352	Not known	64%	11.4 months	Not known	34%	63%
	Vemurafenib 960 mg BID		352		51%	7.3 months	Not known	32%	59%
coBRIM (23)	Cobimetinib 60 mg/d Vemurafemib 960 mg BID	IIIC-IV BRAF-V600 mutation	247	14.2 months	70%	12.3 months	22.	46%	59%
	PlaceboVemurafenib 960 mg BID		248		50%	7.2 months	17.4 months	43%	62%
COLUMBUS (26, 27)	Encorafenib 450 mg/d Binimetinib 45 mg BID	IIIB-IV BRAF-V600 mutation	192	16.6 months	75%	14.9 months	33.6 months	29%	64%
	Encorafenib 300 mg/d		194		58%	9.6 months	23.5 months	24%	62%
	Vemurafenib 960 mg BID		191		49%	7.3 months	16.9 months	27%	65%

BID, twice daily; LDH, lactate dehydrogenase; M1c, distant metastases in a visceral location including the brain or any localization with raised LDH