Combining immune checkpoint inhibitors with standard treatment regimens in advanced human epidermal growth factor receptor-2 positive gastric cancer patients

Table 1 Summary of treatment regimens for control and observation groups

Treatment group	Treatment regimen	Chemotherapy regimen	Immunotherapy option	Dosage and administration
Control group	Standard treatment	XELOX (Oxaliplatin + Capecitabine)		Trastuzumab (6 mg/kg IV) on Day 1 of each cycle
		SOX (Oxaliplatin + S-1)
		Cisplatin + taxane
Observation group	Combination of standard treatment + ICI	XELOX (Oxaliplatin + Capecitabine)	Pembrolizumab (2 mg/kg IV), Camrelizumab (200 mg IV), Sintilimab (200 mg IV)	Pembrolizumab: Day 1 of each cycle; Camrelizumab/Sintilimab: Day 1 of each cycle
		SOX (Oxaliplatin + S-1)		Same as above
		Cisplatin + Nab-Paclitaxel

Table 2 Baseline characteristics, n (%)

	Control (n = 54)	Observation (n = 50)	χ2	P value
Gender			0.198	0.655
Male	43 (79.63)	38 (76.00)
Female	11 (20.37)	12 (24.00)
Age (years)			0.025	0.873
< 65	30 (55.56)	27 (54.00)
≥ 65	24 (44.44)	23 (46.00)
ECOG score			0.005	0.938
0	22 (40.74)	20 (40.00)
1-2	32 (59.26)	30 (60.00)
Tumor location			1.801	0.179
Stomach	21 (38.89)	26 (52.00)
Gastroesophageal junction	33 (61.11)	24 (48.00)
Surgical status			1.874	0.171
Yes	10 (18.52)	15 (30.00)
No	44 (81.48)	35 (70.00)
Liver metastasis			0.063	0.801
Yes	24 (44.44)	21 (42.00)
No	30 (55.56)	29 (58.00)
Peritoneal metastasis			0.068	0.793
Yes	16 (29.63)	16 (32.00)
No	38 (70.37)	34 (68.00)
HER-2 expression			0.497	0.480
IHC2 + (ISH positive)	18 (33.33)	20 (40.00)
IHC3 +	36 (66.67)	30 (60.00)
PD-L1 expression			0.292	0.588
Positive (CPS ≥ 1%)	22 (40.74)	23 (46.00)
Negative (CPS < 1%)	32 (59.26)	27 (54.00)
Chemotherapy regimen
XELOX	23 (42.59)	31 (62.00)
SOX	26 (48.15)	13 (26.00)
Cisplatin + Taxanes	5 (9.26)
Cisplatin + Nab-Paclitaxel		6 (12.00)

ECOG: Eastern Cooperative Oncology Group; HER-2: Human epidermal growth factor receptor 2; IHC: Immunohistochemistry; ISH: In situ hybridization; PD-L1: Programmed death-ligand 1; CPS: Combined positive score.

Table 3 Comparison of grade 1-2 adverse reactions, n (%)

Adverse reaction	Control (n = 54)	Observation (n = 50)	χ2	P value
Leukopenia	22 (40.74)	20 (40.00)	0.005	0.938
Neutropenia	13 (24.07)	19 (38.00)	2.363	0.124
Lymphopenia	28 (51.85)	29 (58.00)	0.396	0.529
Thrombocytopenia	29 (53.70)	25 (50.00)	0.142	0.705
Hemoglobin reduction	23 (42.59)	22 (44.00)	0.020	0.885
Gastrointestinal reaction	20 (37.04)	17 (34.00)	0.104	0.746
Abnormal liver function	9 (16.67)	8 (16.00)	0.008	0.927
Pneumonia	4 (7.41)	3 (6.00)	0.011	0.916
Hypothyroidism	0 (0.00)	6 (12.00)	4.846	0.027

Table 4 Comparison of grade 3-4 adverse reactions, n (%)

Adverse reaction	Control (n = 54)	Observation (n = 50)	χ2	P value
Leukopenia	5 (9.26)	2 (4.00)	0.459	0.497
Neutropenia	9 (16.67)	2 (4.00)	4.404	0.035
Lymphopenia	7 (12.96)	6 (12.00)	0.022	0.882
Thrombocytopenia	9 (16.67)	10 (20.00)	0.193	0.660
Hemoglobin reduction	4 (7.41)	2 (4.00)	0.104	0.746
Gastrointestinal reaction	2 (3.70)	0 (0.00)	0.000	1.000
Abnormal liver function	0 (0.00)	2 (4.00)	0.000	1.000
Pneumonia	0 (0.00)	1 (2.00)	0.000	1.000
Hypothyroidism	0 (0.00)	0 (0.00)	0.000	1.000

Table 5 Univariate and multivariate analysis of progression-free survival in advanced human epidermal growth factor receptor 2-positive gastric cancer

Factor	n = 104	mPFS (months)	Univariate analysis			Multivariate analysis
			HR	95%CI	P value	HR	95%CI	P value
Gender			0.961	0.558-1.657	0.894
Male	81	7.8
Female	23	7.4
Age (years)			0.746	0.469-1.181	0.203
< 65	57	6.6
≥ 65	47	9.1
ECOG score			1.972	1.208-3.199	0.005	2.014	1.231-3.265	0.004
0	42	11.6
1-2	62	6.7
Tumor location			1.048	0.663-1.652	0.847
Stomach	47	7.9
Gastroesophageal Junction	57	7.6
Surgical status			1.299	0.765-2.214	0.335
Yes	25	6.6
No	79	7.8
Liver metastasis			1.125	0.708-1.767	0.623
Yes	45	6.8
No	59	7.9
Peritoneal metastasis			3.782	2.256-6.343	< 0.001	3.767	2.249-6.285	< 0.001
Yes	32	4.2
No	72	9.3
HER-2 expression			0.779	0.485-1.248	0.300
IHC2 + (ISH positive)	38	7.6
IHC3 +	66	7.9
PD-L1 expression			1.847	1.159-2.874	0.046	2.158	1.325-3.131	0.017
Positive (CPS ≥ 1%)	45	8.9
Negative (CPS < 1%)	59	4.5
Chemotherapy regimen			1.592	1.003-2.569	0.049	1.731	1.074-2.775	0.026
Combined immunotherapy	50	9.3
Non-combined Immunotherapy	54	6.7

ECOG: Eastern Cooperative Oncology Group; HER-2: Human epidermal growth factor receptor 2; IHC: Immunohistochemistry; ISH: In situ hybridization; PD-L1: Programmed death-ligand 1; CPS: Combined positive score; mPFS: Median progression-free survival; HR: Hazard ratio; CI: Confidence interval.