Impact of KRAS Mutations on Management of Colorectal Carcinoma

Table 2

Clinical trials with retrospective subset analyses of antiEGFR efficacy in relation to KRAS mutation status.

Study	Setting	Treatment	KRAS genotype	No. of patients	ORR (%)	mPFS (mos)	mOS (mos)
Single arm studies
Lièvre et al. [34]	Second-line treatment	Cetuximab	WT; Mut	65; 24	40*; 0	31.4 wk*; 10.1	14.3*; 10.1
De Roock et al. [29]	Irinotecan refractory	Cetuximab or cetuximab + irinotecan	WT; Mut	57; 46	41^†; 0	34 wk^† (combo) 12 (cetux); 12	44.7 wk^† (combo) 27 wk (cetux); 25.3–27.3
Khambata-Ford et al. [28]	Second or third-line treatment	Cetuximab	WT; Mut	50; 30	10; 0	N.R.	N.R.
Di Fiore et al. [47]	Refractory disease	Cetuximab + chemotherapy	WT; Mut	43; 16	20.3; 0	N.R.	N.R.
Benvenuti et al. [48]	Various lines of treatment	Cetuximab or panitumumab or cetuximab + chemotherapy	WT; Mut	32; 16	31; 6	N.R.	N.R.
Randomized studies
Amado et al. [24]	Refractory disease	Panitumumab + BSC vs. BSC	WT; Mut vs.; WT; Mut	124; 84; 119; 100	17; 0; 0; 0	12.3 wk*; 7.4 wk; 7.3 wk; 7.3 wk	8.1; 4.9; 7.6; 4.4
Van Cutsem et al. [33]	First-line treatment	FOLFIRI + cetuximab vs. FOLFIRI	WT; Mut vs.; WT; Mut	172; 105; 176; 87	59.3; 36.2; 43.2; 40.2	9.9*; 7.6; 8.7; 8.1	24.9; 17.5; 21.0; 17.7
Van Cutsem et al. [42]	First-line treatment	FOLFIRI + cetuximab vs. FOLFIRI	WT; Mut vs.; WT; Mut	316; 214; 350; 183	57.3*; 31.3; 39.7; 36.1	9.9*; 7.4; 8.4; 7.7	23.5*; 16.2; 20.0; 16.7
Bokemeyer et al. [31]	First-line treatment	FOLFOX + cetuximab vs. FOLFOX	WT; Mut vs.; WT; Mut	61; 52; 73; 47	61*; 33; 37; 49	7.7*; 5.5; 7.2; 8.6	N.R.
Bokemeyer et al. [43]	First-line treatment	FOLFOX + cetuximab vs. FOLFOX	WT; Mut vs.; WT; Mut	82; 77; 97; 59	57*; 34; 34; 53	8.3*; 5.5; 7.2; 8.6	22.8; 18.5; 13.4; 17.5
Karapetis et al. [35]	Refractory disease	Cetuximab + BSC vs. BSC	WT; Mut vs.; WT; Mut	115; 81; 113; 83	12.8; 1.2; 0; 0	3.7*; 1.8; 1.9; 1.8	9.5*; 4.5; 4.8; 4.6
Siena et al. [44]	First-line treatment	FOLFOX + panitumumab vs. FOLFOX	WT = 656; Mut = 440		55; 48	9.6 (wt)*; 7.3 (mut); 8.0 (wt); 8.8 (mut)	N.R.
Kohne et al. [45]	First-line treatment	FOLFIRI + panitumumab	WT; Mut	85; 57	48; 29	N.R.	N.R.
Tol et al. [49]	First-line treatment	CAPOX + bevacizumab + cetuximab vs. CAPOX + bevacizumab	WT; Mut; WT; Mut	158; 98; 156; 108	50.0; 59.2; 61.4*; 45.9	10.5*; 8.1; 10.6; 12.5	21.8; 17.2; 22.4; 24.9
Hecht et al.[50]	First-line treatment	FOLFOX + bevacizumab + panitumumab vs. FOLFOX + bevacizumab	WT; Mut; WT; Mut	201; 135; 203; 125	50; 47; 56; 44	9.8; 10.4; 11.5; 11.0	20.7; 19.3; 24.5; 19.3

*Statistically significant improvement
^†Statistically significant improvement for the combination of cetuximab and irinotecan only.
ORR: overall response rate; mPFS: median progression-free survival; mOS: median overall survival; N.R.: not reported; BSC: best supportive care.