Overall survival with frontline vs subsequent anti-epidermal growth factor receptor therapies in unresectable, RAS/BRAF wild-type, left-sided metastatic colorectal cancer

Table 1 Demographic and clinical characteristics between frontline and subsequent-line anti-epidermal growth factor receptor groups, n (%)

Characteristics	All (n = 222)	Frontline anti-EGFR (n = 74)	Subsequent-line anti-EGFR (n = 148)	P value
Age at diagnosis
Median (range), years	60 (26-92)	61 (26-83)	59.5 (30-92)
≥ 65 years	65 (29.3)	24 (32.4)	41 (27.7)	0.465
Sex
Male	144 (64.9)	49 (66.2)	95 (64.2)
Female	78 (35.1)	25 (33.8)	53 (35.8)	0.766
ECOG
0	35 (15.8)	9 (12.2)	26 (17.6)
1	182 (82)	64 (86.5)	118 (79.7)	0.452
2	5 (2.3)	1 (1.4)	4 (2.7)
Underlying disease
No	107 (48.2)	43 (58.1)	64 (43.2)	0.037
Hypertension	76 (34.2)	17 (23)	59 (39.9)	0.012
Diabetes	44 (19.8)	13 (17.6)	31 (20.9)	0.552
Dyslipidemia	48 (21.6)	17 (23)	31 (20.9)	0.729
Cerebrovascular disease	8 (3.6)	3 (4.1)	5 (3.4)	0.799
Ischemic heart disease	7 (3.2)	3 (4.1)	4 (2.7)	0.587
Other cancers	6 (2.7)	4 (5.4)	2 (1.4)	0.079
Tumor location
Splenic flexure	7 (3.2)	1 (1.4)	6 (4.1)	0.032
Descending colon	21 (9.5)	9 (12.2)	12 (8.1)
Sigmoid colon	118 (53.2)	41 (55.4)	77 (52)
Rectosigmoid	25 (11.3)	11 (14.9)	14 (9.5)
Rectum	51 (23)	12 (16.2)	39 (26.4)
Histologic subtype				0.409
Mucinous adenocarcinoma	3 (1.4)	2 (2.7)	1 (0.7)
Signet ring cell carcinoma	2 (0.9)	1 (1.4)	1 (0.7)
Tumor grade				0.596
Well differentiated	63 (33.7)	22 (36.7)	41 (32.3)
Moderately differentiated	109 (58.3)	32 (53.3)	77 (60.6)
Poorly differentiated	15 (8)	6 (10)	9 (7.1)
Metastatic type				0.109
Synchronous	189 (85.1)	67 (90.5)	122 (82.4)
Metachronous	33 (14.9)	7 (9.5)	26 (17.6)
Number of metastatic sites				0.053
1	133 (59.9)	53 (71.6)	80 (54.1)
2	67 (30.2)	18 (24.3)	49 (33.1)
3	13 (5.9)	2 (2.7)	11 (7.4)
≥ 4	9 (4.1)	1 (1.4)	8 (5.4)
Site of metastasis
Liver	172 (77.5)	63 (85.1)	109 (73.6)	0.053
Liver-limited metastasis	97 (43.7)	46 (42.2)	51 (34.5)	< 0.001
Lung	65 (29.3)	13 (17.6)	52 (35.1)	0.007
Peritoneum	49 (22.1)	13 (17.6)	36 (24.3)	0.252
Distant lymph nodes	30 (13.5)	6 (8.1)	24 (16.2)	0.096
MMR or MSI status				0.265
MMR deficient/high MSI	3 (1.4)	1 (1.4)	2 (1.4)
MMR proficient/stable MSI	101 (45.5)	28 (37.8)	73 (49.3)
Unknown	118 (53.2)	45 (60.8)	73 (49.3)
Line of anti-EGFR				< 0.001
1	74 (33.3)	74 (100)	-
2	47 (21.2)	-	47 (31.8)
3	75 (33.8)	-	75 (50.7)
4	19 (8.6)	-	19 (12.8)
5	7 (3.2)	-	7 (4.7)
Retreatment anti-EGFR	53 (23.9)	25 (33.8)	28 (18.9)	0.014
Line of bevacizumab
1	51 (23)	-	51 (34.5)	< 0.001
2	75 (33.8)	25 (33.8)	50 (33.8)	1
3	22 (9.9)	7 (9.5)	15 (10.1)	0.874
4	16 (7.2)	5 (6.8)	11 (7.4)	0.854
5	6 (2.7)	2 (2.7)	4 (2.7)	1
Any lines of bevacizumab	143 (64.4)	33 (44.6)	110 (74.3)	< 0.001
Regimen chemotherapy at first-line				0.166
5FU/Capecitabine	5 (2.3)	-	5 (3.4)
FOLFOX/CAPEOX	167 (75.2)	55 (74.3)	112 (75.7)
FOLFIRI/CAPIRI	47 (21.2)	19 (25.7)	28 (18.9)
FOLFOXIRI/mFOLFORINOX	3 (1.4)	-	3 (2)
Line number of systemic treatments
Median (range)	3 (1-8)	2.5 (1-7)	4 (2-8)	< 0.001
1	21 (9.5)	21 (28.4)	-
2	34 (15.3)	18 (21.6)	18 (12.2)
3	63 (28.4)	19 (25.7)	44 (29.7)
4	56 (25.2)	10 (13.5)	46 (31.1)
≥ 5	48 (21.6)	8 (10.8)	40 (27)
Local treatment at metastatic sites	122 (55)	51 (68.9)	71 (48)	0.003
Metastectomy at liver	73 (32.9)	38 (51.4)	35 (23.6)	< 0.001
Patient status at last follow-up
No evidence of disease	13 (5.9)	11 (14.9)	2 (1.4)	< 0.001
Alive with disease	51 (23)	18 (24.3)	33 (22.3)
Death	157 (70.7)	44 (59.5)	113 (76.4)
Unknown	1 (0.5)	1 (1.4)	-

Median follow up time: 29 months, cut-off date of data: June 30, 2024. EGFR: Epidermal growth factor receptor; MMR: Mismatch repair; MSI: Microsatellite instability; ECOG: Eastern Cooperative Oncology Group.

Table 2 Univariate and multivariate analysis by Cox regression analysis for overall survival in patients receiving anti-epidermal growth factor receptor therapy

Covariate	Univariate			Multivariate
	HR	95%CI	P value	HR	95%CI	P value
Age
≥ 65 vs < 65 years	0.83	0.56-1.16	0.242	NA	NA	NA
Female vs male	0.9	0.65-1.25	0.525	NA	NA	NA
ECOG PS
1 vs 0	1.06	0.70-1.62	0.78	NA	NA	NA
2 vs 0	1.19	0.41-3.42	0.748
Underlying disease
Yes vs no	0.91	0.66-1.24	0.54	NA	NA	NA
Histologic subtype
Mucinous vs adenocarcinoma	0.67	0.17-2.72	0.575	0.35	0.08-1.43	0.142
Signet ring cell vs adenocarcinoma	10.74	2.58-44.74	0.001	9.79	2.31-41.57	0.002
Tumor grade
Moderately vs well differentiated	1.12	0.76-1.65	0.557	0.98	0.64-1.50	0.92
Poorly vs well differentiated	2.38	1.24-4.58	0.009	2.18	1.07-4.43	0.032
Metastatic type
Metachronous vs synchronous	0.92	0.59-1.42	0.696	NA	NA	NA
Number of metastases
≥ 2 vs 1 site	1.44	1.05-1.98	0.024	1.44	0.87-2.39	0.161
Liver-limited metastasis
Yes vs no	0.6	0.43-0.84	0.002	1.71	0.92-3.17	0.088
Peritoneal metastasis
Yes vs no	1.85	1.30-2.63	< 0.001	1.31	0.84-2.03	0.233
Anti-EGFR approach
Frontline vs subsequent-line	1.03	0.73-1.46	0.878	1.12	0.79-1.82	0.393
First-line bevacizumab
Yes vs no	0.92	0.64-1.32	0.66	NA	NA	NA
Metastectomy at liver
Yes vs no	0.32	0.22-0.47	< 0.001	0.25	0.15-0.42	< 0.001

ECOG: Eastern Cooperative Oncology Group.