Efficacy and Safety of Maintenance Therapy Using Cetuximab in Patients with Metastatic Colorectal Cancer: Retrospective Study

Figures & data

Figure 1 Inclusion criteria and treatment pattern.

Table 1 Clinicopathological and Disease Characteristics of 81 Metastatic Colorectal Cancer Patients with Disease Control After Induction Treatment (Chemotherapy Combined with CET) at Baseline

Characteristics	Total (N=81) (%)
Gender
Male	61 (75.3)
Female	20 (24.7)
Median age (range), years
Median age (range)	64 (22, 83)
≤65	43 (53.1)
>65	38 (46.9)
ECOG performance status before induction therapy
0–1	79 (97.5)
≥2	2 (2.5)
Primary tumor location
Left side	78 (96.3)
Right side	3 (3.7)
MMR or MSI status
pMMR or MSS	81 (100)
dMMR or MSI-H	0 (0)
Peritoneal metastasis
No	67 (82.7)
Yes	14 (17.3)
Surgical resection of primary tumor
Yes	61 (75.3)
No	20 (24.7)
Induction chemotherapy regimen
CET+mFOLFOX6	39 (48.1)
CET+FOLFIRI	32 (39.5)
CET+mXELIRI	10 (12.3)
Best overall response during induction therapy
CR/PR	49 (60.5)
SD	32 (39.5)

Abbreviation: CET, Cetuximab.

Table 2 Treatment Modes After Induction Therapy

Treatment Modes	Number of Patients (%)
All patients	N=81
Observation	20 (24.7)
Maintenance	61 (75.3)
Maintenance group	N=61
CET	21 (34.4)
CET+ chemotherapy	40 (65.6)
CET+CF	5 (8.2)
CET+ irinotecan	15 (24.6)
CET+ capecitabine	20 (32.8)
Dose reduction during maintenance	12 (19.7)
Maintenance discontinuation
Due to disease progression	37 (60.7)
Due to AEs	12 (19.7)

Abbreviation: AEs, adverse events.

Table 3 Univariate Analyses for PFS and PFS During Maintenance Therapy/Observation (mnPFS)

Characteristics	PFS		mnPFS
	HR (95% CI)	p-value	HR (95% CI)	p-value
Gender		0.801		0.413
Male	1.000 (reference)		1.00 (reference)
Female	1.084 (0.578, 2.034)		1.296 (0.697, 2.410)
Median age (range), years		0.441		0.134
≤65	1.00 (reference)		1.00 (reference)
>65	0.810 (0.474, 1.384)		1.517 (0.879, 2.617)
ECOG performance status before induction therapy		0.309		0.219
0–1	1.00 (reference)		1.00 (reference)
≥2	2.992 (0.362, 24.743)		0.265 (0.032, 2.200)
Primary tumor location		0.823		0.609
Left side	1.00 (reference)		1.00 (reference)
Right side	1.140 (0.361, 3.599)		1.366 (0.414, 4.501)
Peritoneal metastasis or not		0.011		0.036
No	1.00 (reference)		1.00 (reference)
Yes	2.467 (1.23, 4.94)		2.099 (1.050, 4.196)
Surgical resection of primary tumor		0.718		0.817
Yes	1.00 (reference)		1.00 (reference)
No	0.900 (0.506, 1.599)		1.072 (0.596, 1.929)
Chemotherapy regimen
CET+mFOLFOX6	1.00 (reference)		1.00 (reference)
CET+FOLFIRI	0.783 (0.452, 1.356)	0.383	0.900 (0.520, 1.557)	0.707
CET+mXELIRI	0.973 (0.434, 2.180)	0.947	1.225 (0.536, 2.803)	0.630
Best overall response during induction therapy		0.050		0.015
SD	1.00 (reference)		1.00 (reference)
PR/CR	0.591 (0.349, 1.001)		0.511 (0.297, 0.879)
Treatment Modes after induction therapy		0.041		0.044
Observation	1.00 (reference)		1.00 (reference)
Maintenance	0.541 (0.299, 0.976)		0.536 (0.293, 0.982)

Table 4 Multivariate Analyses for PFS and PFS During Maintenance Therapy/Observation (mnPFS)

Characteristics	PFS		mnPFS
	HR (95% CI)	p-value	HR (95% CI)	p-value
Peritoneal metastasis or not		0.003		0.012
No	1.00 (reference)		1.00 (reference)
Yes	2.521 (1.355, 4.689)		2.213 (1.189, 4.120)
Best overall response during induction therapy		0.013		0.001
SD	1.00 (reference)		1.00 (reference)
PR/CR	0.536 (0.327, 0.878)		0.461 (0.280, 0.757)
Treatment Modes after induction therapy		0.021		0.044
Observation	1.00 (reference)		1.00 (reference)
Maintenance	0.510 (0.288, 0.904)		0.549 (0.307, 0.983)

Table 5 Univariate Analyses for PFS and mnPFS with Maintenance Therapy

Characteristics	PFS		mnPFS
	HR (95% CI)	p-value	HR (95% CI)	p-value
Maintenance therapy regimen		0.313		0.251
CET	1.00 (reference)		1.00 (reference)
CET+ chemotherapy	0.747 (0.424, 1.316)		0.719 (0.409, 1.263)

Figure 2 Kaplan-Meier plot of progression-free survival (PFS) and log-rank analysis of predictors of CET-based treatment in mCRC patients (n = 81 for a to d, n = 61 for e). (a) All patients (b) Maintenance/Observation (c) Best overall response during induction therapy (d) Peritoneal metastasis (e) Maintenance therapy regimen.

Figure 3 Kaplan-Meier plot of PFS during maintenance/observation (mnPFS) and log-rank analysis of predictors of CET-based treatment in mCRC patients (n = 81 for a to d, n = 61 for e). (a) All patients (b) Maintenance/Observation (c) Best overall response during induction therapy (d) Peritoneal metastasis (e) Maintenance therapy regimen.

Table 6 Adverse Events Related to Treatment

AE	Induction Phase (N/%)N=81	Maintenance Phase N=61
		CET (N/%)	CET+ Chemo (N/%)	p-value
		N=21	N=40
Diarrhea
All grade	22 (27.2)	2 (9.5)	8 (20.0)	0.294
Grade 3–4	4 (4.9)	0 (0)	0 (0)	–
Hand-foot syndrome
All grade	18 (22.2)	7 (33.3)	10 (25.0)	0.490
Grade 3–4	3 (3.7)	0 (0)	1 (2.5)	0.465
Rash acneiform
All grade	57 (70.3)	12 (57.1)	26 (65.0)	0.547
Grade 3–4	9 (11.1)	1 (4.8)	1 (2.5)	0.637
Anemia
All grade	26 (32.1)	2 (9.5)	9 (22.5)	0.210
Grade 3–4	2 (2.5)	0 (0)	1 (2.5)	0.465
Nausea & vomiting
All grade	55 (67.9)	1 (4.8)	11 (27.5)	0.034
Grade 3–4	4 (4.9)	0 (0)	0 (0)	–
Fatigue
All grade	69 (85.2)	5 (23.8)	22 (55.0)	0.020
Grade 3–4	9 (11.1)	0 (0)	1 (2.5)	0.465
Oral mucositis
All grade	9 (11.1)	3 (14.3)	8 (20.0)	0.581
Grade 3–4	2 (2/5)	1 (4.8)	0 (0)	0.164
Neutropenia
All grade	65 (80.2)	2 (9.5)	17 (42.5)	0.008
Grade 3–4	7 (8.6)	0 (0)	3 (7.5)	0.198
Hepatotoxicity
All grade	16 (19.8)	3 (14.3)	9 (22.5)	0.443
Grade 3–4	1 (1.2)	0 (0)	0 (0)	–