Chemotherapy plus bevacizumab with or without anti-programmed death 1 immunotherapy as the second-line therapy in colorectal cancer

doi:10.3748/wjg.v31.i21.106939

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World Journal of Gastroenterology

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Retrospective Cohort Study

World J Gastroenterol. Jun 7, 2025; 31(21): 106939
Published online Jun 7, 2025. doi: 10.3748/wjg.v31.i21.106939

Table 1 Baseline characteristics and treatment details of patients in the matched cohort, n (%)

Characteristics	Levels	Control group (n = 77)	Experiment group (n = 26)	P value
Age	> 60	33 (42.9)	12 (46.2)	0.949
Age	≤ 60	44 (57.1)	14 (53.8)	0.949
Gender	Male	55 (71.4)	18 (69.2)	1.000
Gender	Female	22 (28.6)	8 (30.8)	1.000
ECOG	0-1	69 (89.6)	22 (84.6)	0.739
ECOG	2	8 (10.4)	4 (15.4)	0.739
Primary tumor location	Right colon	20 (26)	9 (34.6)	0.552
Primary tumor location	Left colon and rectum	57 (74)	17 (65.4)	0.552
Primary tumor surgery	No	15 (19.5)	3 (11.5)	0.533
Primary tumor surgery	Yes	62 (80.5)	23 (88.5)	0.533
Number of metastatic organs	1	26 (33.8)	8 (30.8)	0.968
Number of metastatic organs	≥ 2	51 (66.2)	18 (69.2)	0.968
Liver metastasis	No	19 (24.7)	8 (30.8)	0.724
Liver metastasis	Yes	58 (75.3)	18 (69.2)	0.724
Lung metastasis	No	41 (53.2)	11 (42.3)	0.461
Lung metastasis	Yes	36 (46.8)	15 (57.7)	0.461
RAS mutation type	Unknown	15 (19.5)	5 (19.2)	0.872
	Wild-type	12 (15.6)	3 (11.5)
	Mutation	50 (64.9)	18 (69.2)

The control group received chemotherapy combined with bevacizumab; the experimental group received chemotherapy combined with bevacizumab and anti- programmed death 1 immunotherapy. ECOG: Eastern Cooperative Oncology Group.

Table 2 Comparison of short-term efficacy between two groups of microsatellite stable metastatic colorectal cancer

Group	Number	PR	SD	PD	DCR (%)
Control group	77	7	34	36	57.14
Experimental group	26	3	17	6	76.92
χ² value	-	-	2.706	3.585	3.5847
P value	-	0.71¹	0.1	0.058	0.058

¹Fisher’s exact test.

Table 3 Univariate and multivariate Cox analysis of the effect of prognostic factors in the original cohort, n (%)

Dependent: Survival (PFS/30, status)		All patients (n = 131)	HR (univariable)	HR (multivariable)
Gender	Male	76 (58.0)	-	-
Gender	Female	55 (42.0)	0.87 (0.60-1.26, P = 0.458)	-
Age	> 60	66 (50.4)	-	-
Age	≤ 60	65 (49.6)	0.73 (0.50-1.07, P = 0.110)	-
ECOG	0-1	116 (88.5)	-	-
ECOG	2	15 (11.5)	1.34 (0.73-2.47, P = 0.340)	-
Number of metastatic organs	1	55 (42.0)	-	-
Number of metastatic organs	≥ 2	76 (58.0)	1.96 (1.32-2.90, P < 0.001)	1.90 (1.27-2.84, P = 0.002)
Primary tumor location	Right colon	32 (24.4)	-	-
Primary tumor location	Left colon and rectum	99 (75.6)	0.92 (0.61-1.40, P = 0.697)	-
Liver metastasis	No	46 (35.1)	-	-
Liver metastasis	Yes	85 (64.9)	1.57 (1.04-2.36, P = 0.032)	1.28 (0.84-1.96, P = 0.254)
Lung metastasis	No	70 (53.4)	-	-
Lung metastasis	Yes	61 (46.6)	1.23 (0.85-1.78, P = 0.274)	-
RAS mutation type	Unknown	25 (19.1)	-	-
	Wild type	20 (15.3)	0.97 (0.51-1.85, P = 0.930)	-
	Mutation	86 (65.6)	1.37 (0.84-2.24, P = 0.202)	-
Group	Control group	105 (80.2)	-	-
Group	Experimental group	26 (19.8)	0.51 (0.31-0.82, P = 0.006)	0.49 (0.30-0.80, P = 0.004)

n = 131, events = 115, likelihood ratio test = 22.56 on 3 df (P < 0.001). ECOG: Eastern Cooperative Oncology Group; PFS: Progression-free survival; HR: Hazard ratio.

Table 4 Treatment-emergent adverse events in the 103 patients of the matched dataset, n (%)

Toxicities	Experimental group (n = 26)			Control group (n = 77)			P value for grade 1-2	P value for grade 3-4
Toxicities	Grade 0	Grade 1-2	Grade 3-4	Grade 0	Grade 1-2	Grade 3-4	P value for grade 1-2	P value for grade 3-4
Anemia	8 (30.8)	15 (57.7)	3 (11.5)	47 (61.0)	29 (37.7)	1 (1.3)	0.1197^a	0.2451^b
Neutropenia	18 (69.2)	7 (26.9)	1 (3.8)	58 (75.3)	14 (18.2)	5 (6.5)	0.4996^a	1^b
Leukocytopenia	14 (53.8)	11 (42.3)	1 (3.8)	55 (71.4)	18 (23.4)	4 (5.2)	0.1088^a	0.3667^b
Thrombocytopenia	17 (65.4)	9 (34.6)	0 (0.0)	62 (80.5)	15 (19.5)	0 (0.0)	0.1902^a	1^b
Proteinuria	21 (80.8)	5 (19.2)	0 (0.0)	70 (90.9)	7 (9.1)	0 (0.0)	0.2984^a	1^b
Aspartate transaminase increased	18 (69.2)	7 (26.9)	1 (3.8)	56 (72.7)	20 (26.0)	1 (1.3)	1^a	1^b
Alanine transaminase increased	20 (76.9)	5 (19.2)	1 (3.8)	65 (84.4)	12 (15.6)	0 (0.0)	0.8985^a	1^b
Alkaline phosphatase increased	21 (80.8)	5 (19.2)	0 (0.0)	69 (89.6)	7 (9.1)	1 (1.3)	0.1732^b	1^b
Blood bilirubin increased	20 (76.9)	5 (19.2)	1 (3.8)	61 (79.2)	16 (20.8)	0 (0.0)	1^a	1^b
Triglycerides increased	20 (76.9)	4 (15.4)	2 (7.7)	67 (87.0)	10 (13.0)	0 (0.0)	0.7475^b	0.4967 ^b
Nausea	18 (69.2)	8 (30.8)	0 (0.0)	47 (61.0)	30 (39.0)	0 (0.0)	0.6076^a	1^b
Vomiting	19 (73.1)	7 (26.9)	0 (0.0)	61 (79.2)	16 (20.8)	0 (0.0)	0.7054^a	1^b
Fatigue	18 (69.2)	8 (30.8)	0 (0.0)	68 (88.3)	9 (11.7)	0 (0.0)	0.0332^b	1^b
Fever	24 (92.3)	2 (7.7)	0 (0.0)	73 (94.8)	4 (5.2)	0 (0.0)	0.6407^b	1^b
Diarrhea	24 (92.3)	1 (3.8)	1 (3.8)	71 (92.2)	6 (7.8)	0 (0.0)	0.6759^b	1^b
Peripheral neurotoxicity	25 (96.2)	1 (3.8)	0 (0.0)	77 (100.0)	0 (0.0)	0 (0.0)	0.2524^b	1^b
Hand-foot syndrome	23 (88.5)	3 (11.5)	0 (0.0)	73 (94.8)	4 (5.2)	0 (0.0)	0.3648^b	1^b
Hypertension	24 (92.3)	1 (3.8)	1 (3.8)	72 (93.5)	4 (5.2)	1 (1.3)	1^b	1^b

^aP values were calculated by χ² test.

^bP values were calculated by Fisher’s exact test.

The control group received chemotherapy combined with bevacizumab; the experimental group received chemotherapy combined with bevacizumab and anti-programmed death 1 immunotherapy.

Table 5 Baseline hematological prognostic indicators markers for patients receiving chemotherapy combined with bevacizumab and anti-programmed death 1immunotherapy, mean ± SD

Characteristics	Stats	Normal range
Height (cm)	168.3 ± 8.0	140-190
Weight (kg)	67.7 ± 12.0	40-100
ALLC (10⁹/L)	6.0 ± 1.9	3.5-9.5
RDW (%)	15.2 ± 3.8	11.6-14.8
PLT (10⁹/L)	178.2 ± 63.7	125-350
ANC (10⁹/L)	4.1 ± 1.4	1.8-6.3
ALC (10⁹/L)	1.4 ± 0.5	1.1-3.2
AMC (10⁹/L)	0.4 ± 0.1	0.1-0.6
AEC (10⁹/L)	0.2 ± 0.2	0.02-0.52
ALB (g/L)	41.4 ± 4.0	40-55
LDH (IU/L)	240.0 ± 154.9	109-245
FIB (g/L)	3.6 ± 0.7	2-4
Dimer (ng/ml)	257.3 ± 647.3	0-500
CEA (ng/mL), n (%)	6 (24.0%)	0-5
CEA (ng/mL), n (%)	19 (76.0%)	-
CA199 (IU/mL), n (%)	13 (52.0%)	0-37
CA199 (IU/mL), n (%)	12 (48.0%)	-

ALLC: Absolute leukocyte count; RDW: Red blood cell distribution width; PLT: Platelet; ANC: Absolute neutrophil count; ALC: Absolute lymphocyte count; AMC: Absolute monocyte count; AEC: Absolute eosinophil count; ALB: Albumin; LDH: Lactate dehydrogenase; FIB: Fibrinogen; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199.

Table 6 Univariate and multivariate Cox analysis of prognostic factors in microsatellite stable metastatic colorectal cancer patients receiving chemotherapy combined with bevacizumab and anti-programmed death 1 immunotherapy

Dependent: Survival (PFS/30, status)		All	HR (univariable)	HR (multivariable)
Age	> 60	11 (44.0)	-	-
Age	≤ 60	14 (56.0)	0.20 (0.07-0.62, P = 0.005)	0.27 (0.05-1.48, P = 0.133)
Gender	Male	18 (72.0)	-	-
Gender	Female	7 (28.0)	1.01 (0.40-2.54, P = 0.979)	-
ECOG	1	21 (84.0)	-	-
ECOG	2	4 (16.0)	1.01 (0.23-4.55, P = 0.985)	-
Location	Right colon	9 (36.0)	-	-
Location	Left colon and rectum	16 (64.0)	0.73 (0.31-1.74, P = 0.477)	-
Liver metastasis	No	7 (28.0)	-	-
Liver metastasis	Yes	18 (72.0)	5.23 (1.48-18.50, P = 0.010)	8.15 (1.39-47.83, P = 0.020)
Lung metastasis	No	10 (40.0)	-	-
Lung metastasis	Yes	15 (60.0)	0.62 (0.25-1.51, P = 0.291)	-
RAS mutation type	Unknown	5 (20.0)	-	-
	Wild type	3 (12.0)	0.75 (0.13-4.20, P = 0.742)	-
	Mutation	17 (68.0)	2.30 (0.74-7.14, P = 0.151)	-
CEA	Normal	6 (24.0)	-	-
CEA	Abnormal	19 (76.0)	0.59 (0.21-1.67, P = 0.316)	-
CA199	Normal	13 (52.0)	-	-
CA199	Abnormal	12 (48.0)	3.16 (1.12-8.88, P = 0.029)	1.06 (0.23-4.90, P = 0.942)
NLR	≤ 2.9	13 (52.0)	-	-
NLR	> 2.9	12 (48.0)	1.45 (0.60-3.55, P = 0.410)	-
LMR	≤ 3.63	13 (52.0)	-	-
LMR	> 3.63	12 (48.0)	0.57 (0.23-1.39, P = 0.216)	-
PLR	≤ 121	13 (52.0)	-	-
PLR	> 121	12 (48.0)	1.43 (0.58-3.48, P = 0.436)	-
BMI	≤ 24.9	12 (48.0)	-	-
BMI	> 24.9	13 (52.0)	1.02 (0.43-2.42, P = 0.963)	-
ALI	≤ 260.9	13 (52.0)	-	-
ALI	> 260.9	12 (48.0)	0.30 (0.10-0.85, P = 0.023)	0.50 (0.15-1.64, P = 0.252)
SII	≤ 426.8	13 (52.0)	-	-
SII	> 426.8	12 (48.0)	1.74 (0.72-4.25, P = 0.220)	-
ALLC	≤ 6.0	13 (52.0)	-	-
ALLC	> 6.0	12 (48.0)	1.31 (0.53-3.20, P = 0.559)	-
ANC	≤ 4.1	13 (52.0)	-	-
ANC	> 4.1	12 (48.0)	1.31 (0.53-3.20, P = 0.559)	-
ALC	≤ 1.4	13 (52.0)	-	-
ALC	> 1.4	12 (48.0)	0.61 (0.25-1.50, P = 0.285)	-
AMC	≤ 0.4	13 (52.0)	-	-
AMC	> 0.4	12 (48.0)	0.71 (0.28-1.82, P = 0.473)	-
AEC	≤ 0.2	13 (52.0)	-	-
AEC	> 0.2	12 (48.0)	1.59 (0.65-3.89, P = 0.309)	-
RDW	≤ 15.2	13 (52.0)	-	-
RDW	> 15.2	12 (48.0)	1.04 (0.42-2.57, P = 0.938)	-
LDH	≤ 240.0	13 (52.0)	-	-
LDH	> 240.0	12 (48.0)	3.09 (1.16-8.22, P = 0.024)	5.72 (1.58-20.72, P = 0.008)

n = 25, events = 21, likelihood ratio test = 25.81 on 5 df (P < 0.001). ECOG: Eastern Cooperative Oncology Group; PFS: Progression-free survival; HR: Hazard ratio; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199; NLR: Neutrophil-to-lymphocyte ratio; LMR: Lymphocyte-to-monocyte ratio; PLR: Platelet-to-lymphocyte ratio; BMI: Body mass index; ALI: Advanced lung cancer inflammation index; SII: Systemic immune-inflammation index; ALLC: Absolute leukocyte count; ANC: Absolute neutrophil count; ALC: Absolute lymphocyte count; AMC: Absolute monocyte count; AEC: Absolute eosinophil count; RDW: Red blood cell distribution width; LDH: Lactate dehydrogenase.

Citation: Gao Z, Wang XY, Shen ZG, Liu JH, Wang XY, Wu SK, Jin X. Chemotherapy plus bevacizumab with or without anti-programmed death 1 immunotherapy as the second-line therapy in colorectal cancer. World J Gastroenterol 2025; 31(21): 106939
URL: https://www.wjgnet.com/1007-9327/full/v31/i21/106939.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i21.106939