Rationally designed treatment for metastatic colorectal cancer: Current drug development strategies

Table 1 Completed trials of approved targeted treatments

Drug	Target	Study	Phase patients	Outcome
Bevacizumab	VEGF-A	Bevacizumab in combination with Oxaliplatin-based chemotherapy as first-line therapy in metastatic CRC.	Phase III	Median OS 21.3 mo Bev/chemo arm vs 19.9 mo chemo alone
			n = 1401	(HR = 0.89, 97.5%CI: 0.76-1.03, P = 0.077)
Cetuximab	EGFR	Cetuximab combined with FOLFIRI vs FOLFIRI alone as first line in mCRC.	Phase III n = 599	Median OS for KRAS WT patients: 23.5 mo (97.5%CI: 21.2-26.3) in Cetux/FOLFIRI arm vs 20 mo (97.5%CI: 17.4-21.7) in FOLFIRI alone
Panitumumab	EGFR	Panitumumab with FOLFOX vs FOLFOX alone in first line aCRC	Phase III n = 656	Median OS (KRAS wt) 23.8 mo (97.5%CI: 20.0–27.7) with panitum/FOLFOX vs 19.4 mo (97.5%CI: 17.4-22.6) with FOLFOX alone
Ziv-aflibercept	VEGFA	Addition of Aflibercept to FOLFIRI in patient with mCRC previously treated with Oxaliplatin-based chemotherapy (including patients who received Bevacizumab)	Phase III	Median OS 13.5 mo (97.5%CI: 12.5-14.9) with Aflibercept/FOLFIRI vs 12 mo (97.5%CI: 11-13) with FOLFIRI alone
	VEGFB		n = 1226
	PIGF
Regorafenib	VEGFR -1, -2, -3	Regorafenib monotherapy for previously treated metastatic colorectal cancer vs best supportive care (CORRECT)	Phase III	Median OS 6.5 mo with Regorafenib vs 5 mo for best supportive care (HR = 0.77, 97.5%CI: 0.64-0.94, P = 0.0052)
	TIE2		n = 760
	KIT, RET, RAF1, BRAF, and BRAFV600E
	PDGFR and FGFR

VEGF: Vascular-endothelial growth factor; EGFR: Epidermal growth factor receptor; FGFR: Fibroblast growth factor receptor; PDGFR: Platelet-derived growth factor receptor; mCRC: Metastatic colorectal cancer; OS: Overall survival.