Additional Biomarkers beyond RAS That Impact the Efficacy of Cetuximab plus Chemotherapy in mCRC: A Retrospective Biomarker Analysis

Table 1

Efficacy outcomes according to RAS status and primary tumor location.

	RAS assessble; (n=247)		RAS wild-type; (n=216)		RAS mutant (n=31)		RAS wild-type/; Left-sided; (n=158)		RAS wild-type/; Right-sided; (n=58)
	Cetuximab plus chemotherapy; (n=117)	Chemotherapy alone; (n=130)	Cetuximab plus chemotherapy; (n=103)	Chemotherapy alone; (n=113)	Cetuximab plus chemotherapy; (n=14)	Chemotherapy alone; (n=17)	Cetuximab plus chemotherapy; (n=74)	Chemotherapy alone; (n=84)	Cetuximab plus chemotherapy; (n=29)	Chemotherapy alone; (n=29)
Overall response
CR	2 (1.7%)	1 (0.8%)	2 (1.9%)	1 (0.9%)	0 (0)	0 (0)	2 (2.7%)	1 (1.2%)	0 (0)	0 (0)
PR	67 (57.3%)	38 (29.2%)	64 (62.1%)	32 (28.3%)	3 (21.4%)	6 (35.2%)	49 (66.2%)	24 (28.6%)	15 (58.6%)	8 (27.6%)
SD	30 (25.6%)	47 (36.1%)	24 (23.3%)	42 (37.1%)	6 (42.9%)	6 (35.2%)	16 (21.6%)	32 (38.1%)	8 (27.6%)	10 (34.5%)
PD	17 (14.5%)	40 (30.8%)	12 (11.7%)	35 (31.0%)	5 (35.7%)	4 (23.5%)	8 (10.8%)	26 (31.0%)	4 (13.7%)	9 (31.0%)
Not assessable	1 (0.9%)	4 (3.1%)	1 (1.0%)	3 (2.7%)	0 (0)	1 (5.9%)	1 (1.4%)	1 (1.2%)	0 (0)	2 (6.9%)
ORR, %	59.0	30.0	64.1	29.2	21.4	35.3	68.9	29.8	51.7	27.6
OR	3.35		4.32		0.50		5.23		2.81
95% CI	1.98-5.67		2.44-7.66		0.10-2.52		2.65-10.32		0.94-8.39
p (Chi-square or Fisher’s)	<0.001		<0.001		0.456		<0.001		0.060
p for interaction test			0.014				0.344
Radical resection rate of LM, %	28.2	10.0	31.1	9.7	7.3	11.8	35.1	10.7	20.7	6.9
OR	3.54		4.18		0.58		4.51		3.52
95% CI	176-7.12		1.98-8.84		0.05-7.12		1.95-10.46		0.65-19.17
p (Chi-square or Fisher’s)	<0.001		<0.001		0.835		<0.001		0.128
PFS, months
Median	9.8	5.7	10.2	5.5	6.0	8.9	11.3	5.6	8.1	5.1
95%CI	8.9-11.1	4.1-5.9	9.3-10.7	4.1-5.9	1.3-6.8	5.0-9.0	9.9-12.1	3.9-6.1	5.2-8.8	2.2-5.8
HR	0.61		0.52		1.63		0.46		0.67
95%CI	0.46-0.80		0.39-0.70		0.75-3.54		0.32-0.65		0.39-1.17
p (log-rank)	<0.001		<0.001		0.166		<0.001		0.127
p for interaction test			0.003				0.183
OS, months
Median	30.0	22.8	36.1	21.7	16.8	25.6	48.0	22.5	23.6	16.8
95%CI	18.9-39.1	18.3-25.7	24.6-43.4	18.0-24.0	11.2-20.8	15.1-32.9	-	18.1-23.9	21.7-26.3	4.5-23.5
HR	0.55		0.46		1.94		0.27		0.66
95%CI	0.38-0.80		0.31-0.70		0.75-5.02		0.14-0.50		0.35-1.26
p (log-rank)	0.001		<0.001		0.146		<0.001		0.200
p for interaction test			0.006				0.036

3 early deaths (less than 3 months) and 2 lost to follow-up before the first time evaluation by MDT.
CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; LM, liver metastases; PFS, progression free survival; OS, overall survival; HR, hazard ratio; OR, odds ratio;95% CI, 95% confidence interval. MDT, multidisciplinary team; NE, not evaluable.