Epidermal growth factor receptor and metastatic colorectal cancer: Insights into target therapies

Table 1 Mainly clinical trial and target therapies

Study	Design	Median PFS (mo)	Median OS (mo)	Toxicity (grade 3/4)	Genetic analyses	Response rate
PACCE trial[18]	PMAB + Bev/Ox-CT	10	19.4	Skin rash, diarrhea, infections and pulmonary embolism	KRAS status was determined in 82% tumor samples. Mutations were found in 40%	46%
	+
	PMAB + Bev/Iri-CT
	Bev/Ox-CT	11.4	24.5			48%
	+
	Bev/Iri-CT
Peeters et al[22]	Panitumumab-FOLFIRI (in the WT KRAS subpopulation)	5.9	14.51	Toxicities associated with anti-EGFR therapy	KRAS status was available for 91% of patients: 597 (55%) with wild-type KRAS tumors, and 486 (45%) with mutant KRAS tumors	Improved to 35% vs 10% with the addition of panitumumab
	FOLFIRI (in the WT KRAS subpopulation)	3.9	12.51
PRIME study[28]	Wild-type KRAS stratum Panitumumab +	9.6	23.91	Toxicities associated with anti-EGFR therapy	KRAS results were available for 1100 ( 93%)patients	55%
	FOLFOX (4)
	FOLFOX(4)	8.0	19.71
	Mutant KRAS stratum					48%
	Panitumumab +	7.3	15.51			40%
	FOLFOX (4)
	FOLFOX (4)	8.8	19.31			40%
COIN trial[29]	Ox and 5FU (arm A) in KRAS wild-type tumours	8.61	17.91	NA	565 (43%) had KRAS mutations	57%
	Ox and 5FU plus cetuximab (arm B) in KRAS wild-type tumours	8.61	17.01	Skin rash and gastrointestinal toxic effects		64%
NORDIC-VII[20]	Standard Nordic FLOX (arm A)	7.91	20.41	The regimens were well tolerated	KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%) respectively	41%
	Cetuximab and FLOX (arm B)	8.31	19.71			49%
	Cetuximab combined with intermittent FLOX (arm C)	7.31	20.31			47%

¹Without statistical significance. PFS: Progression-free survival; OS: Overall survival; PMAB: Panitumumab; Bev: Bevacizumab; Ox:CT: Oxaliplatin:based chemotherapy; Iri-CT: Irinotecan-based chemotherapy; 5FU: 5-fluorouracil; FOLFOX/FLOX: Fluorouracil, leucovorin and oxaliplatin; FOLFIRI: Fluorouracil, leucovorin and irinotecan; NA: Not applicable.