Role of targeted therapy in metastatic colorectal cancer

doi:10.4251/wjgo.v8.i9.642

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. Sep 15, 2016; 8(9): 642-655
Published online Sep 15, 2016. doi: 10.4251/wjgo.v8.i9.642

Table 1 Clinical trials of anti-angiogenic therapies in metastatic colorectal cancer

Trial name	Regimens	n	ORR	PFS (mo)	OS (mo)
First-line chemotherapy
AVF2017g	IFL + Bevacizumab	402	44.8%	10.6	20.3
BICC-C	FOLFIRI + Bevacizumab	57	57.9%	11.2	28.0
NO16966	FOLFOX/CapeOX + Bevacizumab	699	38%	9.4	21.3
TREE-1/2	FOLFOX + Bevacizumab	71	52%	9.9	26.1
CAIRO2	CapeOX + Bevacizumab	378	50%	10.7	20.3
SOFT	SOX + Bevacizumab	256	61.5%	11.7	29.6
TRIBE	FOLFOXIRI + Bevacizumab	252	65.1%	12.1	31.0
AVEX¹	Capecitabine + Bevacizumab	140	19.3%	9.1	20.7
Second-line, salvage-line chemotherapy, or beyond progression
E3200	FOLFOX + Bevacizumab	286	22.7%	7.3	12.9
ML18147	Chemotherapy + Bevacizumab	410	5.4%	5.7	11.2
C-TASK FORCE	TAS-102 + Bevacizumab	25	4.0%	5.6	11.2
VELOUR	FOLFIRI + Aflibercept	612	19.8%	6.9	13.5
RAISE	FOLFIRI + Ramucirumab	536	13.4%	5.7	13.3
CORRECT	Regorafenib	505	1.0%	1.9	6.4

¹AVEX trial enrolled mCRC patients aged 70 years and older. ORR: Objective response rate; PFS: Progression-free survival; IFL: Bolus 5-fluorouracil/leucovorin/irinotecan; FOLFIRI: Bolus and infusional 5-fluorouracil/leucovorin/irinotecan; FOLFOX: Bolus and infusional 5-fluorouracil/leucovorin/oxaliplatin; CapeOX: Capecitabine/oxaliplatin; SOX: S-1 (tegafur/gimeracil/oteracil)/oxaliplatin; FOLFOXIRI: Infusional 5-fluorouracil/leucovorin/irinotecan/oxaliplatin; OS: Overall survival; mCRC: Metastatic colorectal cancer.

Table 2 Clinical trials of anti-epidermal growth factor receptor therapies in metastatic colorectal cancer with KRAS wild type

Trial name	Regimens	n	ORR	PFS (mo)	OS (mo)
First-line chemotherapy
CRYSTAL	FOLFIRI + Cetuximab	316	57.3%	9.9	23.5
OPUS	FOLFOX + Cetuximab	159	57%	8.3	22.8
COIN	FOLFOX/CapeOX + Cetuximab	362	64%	8.6	17.0
NORDIC-VII	FLOX + Cetuximab	97	46%	7.9	20.1
PRIME	FOLFOX + Panitumumab	325	55%	9.6	23.9
Second-line, salvage-line chemotherapy, or beyond progression
20050181 trial	FOLFIRI + Panitumumab	303	36%	6.7	14.5
PICCOLO	Irinotecan + Panitumumab	230	34%	5.5	10.4
CO.17	Cetuximab	117	13%	3.7	9.5
20020408 trial	Panitumumab	124	17%	12.3 wk	8.1

ORR: Objective response rate; PFS: Progression-free survival; OS: Overall survival; FOLFIRI: Bolus and infusional 5-fluorouracil/leucovorin/irinotecan; FOLFOX: Bolus and infusional 5-fluorouracil/leucovorin/oxaliplatin; CapeOX: Capecitabine/oxaliplatin; FLOX: Bolus 5-fluorouracil/leucovorin/oxaliplatin.

Table 3 Clinical trials comparing anti-epidermal growth factor receptor therapy vs anti-vascular endothelial growth factor therapy in metastatic colorectal cancer with KRAS wild type

Trial name	Regimens	n	ORR	PFS (mo)	OS (mo)
First-line chemotherapy
PEAK	FOLFOX + Panitumumab	142	57.8%	10.9	34.2
	FOLFOX + Bevacizumab	143	53.5%	10.1	24.3
	(HR, P-value)		-	HR = 0.87	HR = 0.62
	(HR, P-value)		-	P = 0.353	P = 0.009
FIRE-3	FOLFIRI + Cetuximab	297	62%	10.0	28.7
	FOLFIRI + Bevacizumab	295	58%	10.3	25.0
	(HR, P-value)		OR = 1.18	HR = 1.06	HR = 0.77
	(HR, P-value)		P = 0.18	P = 0.55	P = 0.017
CALGB/SWOG 80405	Chemotherapy¹ + Cetuximab	578	65.6%	10.4	29.9
	Chemotherapy¹ + Bevacizumab	559	57.2%	10.8	29.0
	(HR, P-value)		P = 0.02	HR = 1.04	HR = 0.925
	(HR, P-value)		P = 0.02	P = 0.55	P = 0.34
Second-line chemotherapy
SPIRITT	FOLFIRI + Panitumumab	91	32%	7.7	18.0
	FOLFIRI + Bevacizumab	91	19%	9.2	21.4
	(HR, P-value)		-	HR = 1.01	HR = 1.06
	(HR, P-value)		-	P = 0.97	P = 0.75

¹Chemotherapy regimens were FOLFOX or FOLFIRI. ORR: Objective response rate; PFS: Progression-free survival; OS: Overall survival; HR: Hazard ratio; OR: Odds ratio; FOLFIRI: Bolus and infusional 5-fluorouracil/leucovorin/irinotecan; FOLFOX: Bolus and infusional 5-fluorouracil/leucovorin/oxaliplatin.

Table 4 Treatment outcome by anti-epidermal growth factor receptor therapy as first-line treatment in metastatic colorectal cancer with RAS wild type

Trial name	Regimens	n	ORR	PFS (mo)	OS (mo)
CRYSTAL	FOLFIRI + Cetuximab	178	66.3%	11.4	28.4
	FOLFIRI	189	38.6%	8.4	20.2
	(HR, P-value)		OR = 3.31	HR = 0.56	HR = 0.69
	(HR, P-value)		P < 0.001	P = 0.0002	P = 0.0024
PRIME	FOLFOX + Panitumumab	259	-	10.1	25.8
	FOLFOX	253	-	7.9	20.2
	(HR, P-value)		-	HR = 0.72	HR = 0.77
	(HR, P-value)		-	P = 0.004	P = 0.009
PEAK	FOLFOX + Panitumumab	88	63.6%	13.0	41.3
	FOLFOX + Bevacizumab	82	60.5%	9.5	28.9
	(HR, P-value)		-	HR = 0.65	HR = 0.63
	(HR, P-value)		-	P = 0.029	P = 0.058
FIRE-3	FOLFIRI + Cetuximab	171	65%	10.4	33.1
	FOLFIRI + Bevacizumab	171	60%	10.2	25.6
	(HR, P-value)		OR = 1.28	HR = 0.93	HR = 0.70
	(HR, P-value)		P = 0.32	P = 0.54	P = 0.011
CALGB/SWOG 80405	Chemotherapy¹ + Cetuximab	270	68.6%	11.4	32.0
	Chemotherapy¹ + Bevacizumab	256	53.8%	11.3	31.2
	(HR, P-value)		P < 0.01	HR = 1.1	HR = 0.9
	(HR, P-value)		P < 0.01	P = 0.31	P = 0.4

Citation: Ohhara Y, Fukuda N, Takeuchi S, Honma R, Shimizu Y, Kinoshita I, Dosaka-Akita H. Role of targeted therapy in metastatic colorectal cancer. World J Gastrointest Oncol 2016; 8(9): 642-655
URL: https://www.wjgnet.com/1948-5204/full/v8/i9/642.htm
DOI: https://dx.doi.org/10.4251/wjgo.v8.i9.642