Propensity score-based real-world study of immune checkpoint inhibitor combination therapy in microsatellite stable/proficient mismatch repair metastatic colorectal cancer

Table 1 Baseline clinicopathological characteristics of patients before and after propensity score matching, n (%)

Variables	Subcategories	All patients (n = 123)	Before PSM			After PSM
			Control group (n = 92)	Experimental group (n = 31)	P value	Control group (n = 62)	Experimental group (n = 31)	P value
Age	< 65	59 (47.97)	45 (48.91)	14 (45.16)	0.878	27 (43.55)	14 (45.16)	1.000
	≥ 65	64 (52.03)	47 (51.09)	17 (54.84)		35 (56.45)	17 (54.84)
Gender	Female	48 (39.02)	35 (38.04)	13 (41.94)	0.864	27 (43.55)	13 (41.94)	1.000
	Male	75 (60.98)	57 (61.96)	18 (58.06)		35 (56.45)	18 (58.06)
ECOG PS	0-1	80 (65.04)	59 (64.13)	21 (67.74)	0.883	41 (66.13)	21 (67.74)	1.000
	2	43 (34.96)	33 (35.87)	10 (32.26)		21 (33.87)	10 (32.26)
Primary tumor location	Right colon	48 (39.02)	33 (35.87)	15 (48.39)	0.306	28 (45.16)	15 (48.39)	0.941
	Left colon	75 (60.98)	59 (64.13)	16 (51.61)		34 (54.84)	16 (51.61)
Primary tumor surgery	No	43 (34.96)	35 (38.04)	8 (25.81)	0.309	18 (29.03)	8 (25.81)	0.935
	Yes	80 (65.04)	57 (61.96)	23 (74.19)		44 (70.97)	23 (74.19)
Histological type	Adenocarcinoma	104 (84.55)	78 (84.78)	26 (83.87)	1.000	51 (82.26)	26 (83.87)	1.000
	Mucinous adenocarcinoma	19 (15.45)	14 (15.22)	5 (16.13)		11 (17.74)	5 (16.13)
Tumor differentiation	Poorly differentiated	44 (35.77)	31 (33.70)	13 (41.94)	0.541	23 (37.10)	13 (41.94)	0.821
	Moderately to well differentiated	79 (64.23)	61 (66.30)	18 (58.06)		39 (62.90)	18 (58.06)
Lymphovascular perineural invasion	No	80 (65.04)	61 (66.30)	19 (61.29)	0.773	38 (61.29)	19 (61.29)	1.000
	Yes	43 (34.96)	31 (33.70)	12 (38.71)		24 (38.71)	12 (38.71)
Liver metastasis	No	51 (41.46)	39 (42.39)	12 (38.71)	0.881	21 (33.87)	12 (38.71)	0.818
	Yes	72 (58.54)	53 (57.61)	19 (61.29)		41 (66.13)	19 (61.29)
Lung metastasis	No	64 (52.03)	48 (52.17)	16 (51.61)	1.000	31 (50.00)	16 (51.61)	1.000
	Yes	59 (47.97)	44 (47.83)	15 (48.39)		31 (50.00)	15 (48.39)
Number of metastatic organs	1	68 (55.28)	52 (56.52)	16 (51.61)	0.790	33 (53.23)	16 (51.61)	1.000
	≥ 2	55 (44.72)	40 (43.48)	15 (48.39)		29 (46.77)	15 (48.39)
RAS	Unknown	27 (21.95)	19 (20.65)	8 (25.81)	0.816	16 (25.81)	8 (25.81)	0.943
	Wildtype	44 (35.77)	33 (35.87)	11 (35.48)		20 (32.26)	11 (35.48)
	Mutation	52 (42.28)	40 (43.48)	12 (38.71)		26 (41.93)	12 (38.71)

ECOG PS: Eastern Cooperative Oncology Group Performance Status; PSM: Propensity score matching.

Table 2 Tumor response according to RECIST version 1.1 in the two groups

Group	n	PR	SD	PD	ORR	DCR
Control group	92	22 (23.91)	42 (45.65)	28 (30.43)	22 (23.91)	64 (69.57)
Experimental group	31	10 (32.26)	13 (41.94)	8 (25.81)	10 (32.26)	23 (74.19)
P value	0.650	0.356	0.835	0.820	0.356	0.820

PR: Partial response; SD: Stable disease; PD: Progressive disease; ORR: Objective response rate; DCR: Disease control rate.

Table 3 Treatment-related adverse events in the two groups, n (%)

Adverse events	Control group (n = 92)	Experimental group (n = 31)	P value
Myelosuppression	49 (53.26)	18 (58.06)	0.798
Nausea	27 (29.35)	13 (41.94)	0.284
Diarrhea	18 (19.57)	7 (22.58)	0.918
Fatigue	18 (19.57)	6 (19.35)	1.000
Proteinuria	16 (17.39)	3 (9.68)	0.397
Hypertension	7 (7.61)	5 (16.13)	0.302
Hepatic dysfunction	24 (26.09)	10 (32.26)	0.666
Thyroid dysfunction	13 (14.13)	7 (22.58)	0.411
Hand-foot syndrome	8 (8.70)	2 (6.45)	1.000
rCCEP	0 (0.00)	16 (51.61)	< 0.001

rCCEP: Reactive cutaneous capillary endothelial proliferation.

Table 4 Grade ≥ 3 treatment-related adverse events in the two groups, n (%)

Grade ≥ 3 AEs	Control group (n = 92)	Experimental group (n = 31)	P value
Myelosuppression	3 (3.26)	3 (9.68)	0.341
Nausea	3 (3.26)	0 (0.00)	0.730
Diarrhea	3 (3.26)	0 (0.00)	0.730
Fatigue	1 (1.09)	1 (3.23)	1.000
Proteinuria	2 (2.17)	0 (0.00)	0.995
Hypertension	2 (2.17)	0 (0.00)	0.995
Hepatic dysfunction	3 (3.26)	1 (3.23)	1.000
Thyroid dysfunction	0 (0.00)	1 (3.23)	0.566
Hand-foot syndrome	0 (0.00)	0 (0.00)	1.000

AEs: Adverse events.

Table 5 Univariate and multivariate Cox regression analysis of prognostic factors for progression-free survival and overall survival

Variables	Subcategories	PFS-univariate analysis		PFS-multivariate analysis		OS-univariate analysis		OS-multivariate analysis
		P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)
Age	< 65
	≥ 65	0.128	1.414 (0.905-2.211)			0.347	1.248 (0.787-1.981)
Gender	Female
	Male	0.489	1.175 (0.745-1.853)			0.132	1.447 (0.895-2.339)
ECOG	0-1
	2	0.996	1.001 (0.640-1.567)			0.524	0.856 (0.532-1.379)
Primary tumor location	Right colon
	Left colon	< 0.001	0.456 (0.294-0.708)	< 0.001	0.385 (0.243-0.611)	0.436	0.833 (0.525-1.320)
Primary tumor surgery	No
	Yes	0.006	0.532 (0.341-0.831)	0.023	0.591 (0.376-0.929)	0.348	0.797 (0.496-1.281)
Histological type	Adenocarcinoma
	Mucinous adenocarcinoma	0.193	1.454 (0.827-2.556)			0.609	1.176 (0.632-2.187)
Tumor differentiation	Poorly differentiated
	Moderately to well differentiated	0.567	0.877 (0.560-1.374)			0.751	1.083 (0.663-1.766)
Lymphovascular perineural invasion	No
	Yes	0.109	1.455 (0.920-2.302)			0.011	1.819 (1.144-2.892)	0.135	1.430 (0.894-2.286)
Liver metastasis	No
	Yes	0.003	1.996 (1.260-3.164)	0.012	1.830 (1.141-2.937)	< 0.001	3.772 (2.162-6.579)	< 0.001	3.516 (1.998-6.185)
Lung metastasis	No
	Yes	0.362	0.813 (0.521-1.268)			0.087	0.668 (0.422-1.060)
Number of metastatic organs	1
	≥ 2	0.302	1.261 (0.812-1.959)			0.849	1.046 (0.660-1.656)
RAS	Unknown
	Wildtype	0.388	1.313 (0.707-2.436)			0.923	1.034 (0.528-2.024)
	Mutation	0.134	1.566 (0.871-2.815)			0.172	1.532 (0.831-2.826)
Group	Control group
	Experimental group	0.029	0.551 (0.323-0.939)	0.020	0.509 (0.288-0.901)	0.331	0.762 (0.441-1.317)

PFS: Progression-free survival; OS: Overall survival; HR: Hazard ratio; CI: Confidence interval; ECOG: Eastern Cooperative Oncology Group.