Combination Therapies for the Treatment of Advanced Melanoma: A Review of Current Evidence

Table 1

Comparison between the major trials of BRAF inhibitor monotherapy and BRAF/MEK inhibitor combination trials.

Drug + target	Study; (author, date)	Patient number	Phase	Regimen + drugs (doses)	Response rate (%) (CR or PR)	Response duration	Drug related toxicity; G3/4 AEs	Treatment related mortality	Median PFS (months)	OS (months)
Dabrafenib (D) + trametinib (T); BRAFi + MEKi	Flaherty et al., 2012 [7]	247; (162 in part C: combination (2 doses) versus monotherapy)	1/2	Part C groups: D (150 mg bd) + T (2 mg od) versus D (150 mg bd) + T (1 mg od) versus D (150 mg bd)	41; (𝑃=0.03); 27; (𝑃=0.77); 29	10.5 mo; 9.5 mo; 5.6 mo	58%; 48%; 43%	Nil; Nil; Nil	150/2: 9.4; (𝑃<0.001); 150/1: 9.2; (𝑃=0.006); 150: 5.8	NR
LGX818 + MEK162; BRAFi + MEKi	Kefford et al., 2013 [8]	20; (only 7 with at least one postbaseline scan in BRAF naïve group)	1b/2	LGX818 + MEK162; BRAFi naïve and BRAFi pretreated cohorts	Rx naïve: 86%; Pretreated: 22%	NR	NR	NR	NR	NR
Vemurafenib + GDC-0973; BRAFi + MEKi	Gonzalez et al., 2012 [9]	44	1	Vemurafenib + GDC-0973; Vem. naïve and vem. pretreated groups	Vem. naïve: 100%; Pretreated: NR	NR	NR	NR	NR	NR
Vemurafenib versus dacarbazine	Chapman et al., 2011 [10]	675	3	Vemurafenib (960 mg bd) versus dacarbazine (1000 mg/m^2 q3w); Previously untreated	48; 5	NR	NR	NR	5.3; 1.6	NR (13.2)^a; NR (9.6)^a
Dabrafenib versus dacarbazine	Hauschild et al., 2012 [11]	250	3	Dabrafenib (150 mg bd) versus dacarbazine (1000 mg/m^2 q3w) Previously untreated		NR	53%^b; 44%^b	NR	5.1; (𝑃<0.0001); 2.7	NR (18.2)^c; NR (15.6)^c

aUpdated median overall survival presented at a later updated analysis. ^bGrade 2 toxicity or higher. ^cPresented later at an updated analysis. Difference in median OS was not statistically significant.