Clinical efficacy and drug resistance of anti-epidermal growth factor receptor therapy in colorectal cancer

Table 1 Clinical trials of targeted agents in combination with chemotherapy as first-line treatments for metastatic colorectal cancer

Ref.	Year	Population	Patient number	Regimen	Median PFS (mo)	P1	Median OS (mo)	P1	Response rate (%)	P1
CRYSTAL[19]	2009	All	599	FOLFIRI	8.0	0.048	18.6	0.31	38.7	0.0038
			599	FOLFIRI + Cetuximab	8.9		19.9		46.9
		KRAS WT subgroup	350	FOLFIRI	8.4	0.0012	20	0.0093	39.7	< 0.001
			316	FOLFIRI + Cetuximab	9.9		23.5		57.3
		KRAS MT subgroup	183	FOLFIRI	7.7	0.26	16.7	0.75	36.1	0.35
			214	FOLFIRI + Cetuximab	7.4		16.2		31.3
OPUS[12]	2009	All	168	FOLFOX4	7.2	0.62	18	0.91	36	0.064
			169	FOLFOX4 + Cetuximab	7.2		18.3		46
		KRAS WT subgroup	97	FOLFOX4	7.2	0.0064	18.5	0.39	34	0.0027
			82	FOLFOX4 + Cetuximab	8.3		22.8		57
		KRAS MT subgroup	59	FOLFOX4	8.6	0.0153	17.5	0.2	53	0.029
			77	FOLFOX4 + Cetuximab	5.5		13.4		34
COIN[20]	2011	KRAS WT group	367	FOLFOX/XELOX	8.6	0.60	17.9	0.68	57	0.049
			362	FOLFOX/XELOX + Cetuximab	8.6		17		64
		KRAS WT group	127	FOLFOX	9.2	0.056	-	-	-	-
			117	FOLFOX + Cetuximab	9.0		-		-
		KRAS WT group	240	XELOX	8.0	0.56	-	-	-	-
			245	XELOX + Cetuximab	8.4		-		-
		KRAS MT group	268	FOLFOX/XELOX	-	-	14.8	0.8	-	-
			297	FOLFOX/XELOX + Cetuximab	-		13.6		-
NORDIC-VII[21]	2012	All	185	Nordic FLOX (control group)	7.9	-	20.4	-	41	-
			194	FLOX + Cetuximab	8.3	0.31	19.7	0.67	49	0.15
			187	intermittent FLOX + Cetuximab	7.3	NA	20.3	0.79	47	NA
		KRAS WT subgroup	97	Nordic FLOX (control group)	8.7	-	22	-	47	-
			97	FLOX + Cetuximab	7.9	0.66	20.1	0.48	46	0.89
			109	intermittent FLOX + Cetuximab	7.5	NA	21.4	0.66	51	NA
		KRAS MT subgroup	58	Nordic FLOX (control group)	7.8	-	20.4	-	40	-
			72	FLOX + Cetuximab	9.2	0.07	21.1	0.89	49	0.31
			65	intermittent FLOX + Cetuximab	7.2	NA	20.5	0.84	42	NA
CALGB/SWOG[22] 80405 (study is ongoing)	2014	KRAS WT group	578	FOLFIRI or mFOLFOX6 + Cetuximab	10.45	NA	29.93	0.34	-	-
			559	FOLFIRI or mFOLFOX6 + Bevacizumab	10.84		29.04		-
PRIME[8]	2010	KRAS WT group	331	FOLFOX4	8.0	0.02	19.7	0.072	48	0.068
			325	FOLFOX4 + Panitumumab	9.6		23.9		55
		KRAS MT group	219	FOLFOX4	8.8	0.02	19.3	0.068	40	-
			221	FOLFOX4 + Panitumumab	7.3		15.5		40
Hyman et al[37]	2015	BRAF V600 group	10	Vemurafenib	4.5	-	9.3	-	0	-
			27	Vemurafenib + Cetuximab	3.7		7.1		4
Reidy et al[51]	2010	All	23	IMC-A12 (anti-IGF-1R antibody)	5.9	-	5.2	-	0	-
			21	IMC-A12 (anti-IGF-1R antibody) + Cetuximab	6.1		4.5		5
		KRAS WT group	20	IMC-A12 (anti-IGF-1R antibody) + Cetuximab	9.4		10.9		0

¹95%CI. PFS: Progression-free survival; OS: Overall survival; All: All patients group; WT: Wild type; MT: Mutant type; NA: Not available; KRAS: KRAS exon 2, codons 12 and 13; FOLFIRI: Irinotecan, fluorouracil, and leucovorin; FOLFOX: Fluorouracil, leucovorin, and oxaliplatin; XELOX: Capecitabine and oxaliplatin; FLOX: Fluorouracil, leucovorin, and oxaliplatin.