Patient Characteristics
Thirty patients were included in this study, and the baseline characteristics of the patients are shown in Table 1. The median age of the patients was 60.4 years (41-73 years), 24 (80.0%) male patients and 6 (20.0%) female patients. 20 (66.7%) patients had GC adenocarcinoma and another 10 (33.3%) patients had GEJ adenocarcinoma. 30 were all patients with metastases, and patients with metastases to lymph nodes, peritoneum, liver, lung, or other sites accounted for 73.3%, 36.7%, 56.7%, 13.3%, 33.3%.26 (86.7%) patients received sintilimab in combination with apatinib, 2 (6.7%)
patients received sintilimab in combination with anlotinib, and 2 (6.7%) patients received sintilimab in combination with regorafenib. Patients with previous gastrectomy accounted for 66.7%, patients without previous gastrectomy accounted for 33.3%, 9 (30.0%) patients with previous immunotherapy and 21 (70.0%) patients without previous immunotherapy. 3 (10.0%) patients had positive HER-2 status; 20
Table 1 | Baseline demographic and patient characteristics
|
Characteristics
|
No(%)(n=30)
|
Age(years)
|
Median age [range]
|
60.4[41-73]
|
≤60
|
15(50.0%)
|
>60
|
15(50.0%)
|
Gender
|
|
Male
|
24(80.0%)
|
Female
|
6(20.0%)
|
ECOG performance status
|
0-1
|
26(86.7%)
|
2
|
4(13.3%)
|
Primary tumor site
|
|
GC
|
20(66.7%)
|
GEJ
|
10(33.3%)
|
Metastatic site
|
Lymph node
|
22(73.3%)
|
Peritoneum
|
11(36.7%)
|
Liver
|
17(56.7%)
|
Lung
|
4(13.3%)
|
Others
|
10(33.3%)
|
Number of metastatic sites
|
1-2
|
21(70.0%)
|
≥3
|
9(30.0%)
|
MMR or MSI status
|
pMMR or MSS
|
12(40.0%)
|
dMMR or MSI-H
|
1(3.3%)
|
Unknown
|
17(56.7%)
|
PD-L1 expression level
|
PD-L1 CPS<1
|
6(20.0%)
|
PD-L1 CPS>= 1
Unknown
|
2(6.7%)
22(73.3%)
|
EBER
|
Positive
|
3(10.0%)
|
Negative
|
20(66.7%)
|
Unknown
|
7(23.3%)
|
Targeted drug
|
Apatinib
|
26(86.6%)
|
Anlotinib
|
2(6.7%)
|
Regorafenib
|
2(6.7%)
|
Treatment line
|
Second line
|
3(10.0%)
|
Third line
|
16(53.3%)
|
Four or more lines
|
11(36.7%)
|
Treatment course
|
1 course or more
|
6(20.0%)
|
4 courses or more
|
12(40.0%)
|
6 courses or more
|
2(6.7%)
|
8 courses or more
|
10(33.3%)
|
Previous immunotherapy
|
YES
|
9(30.0%)
|
NO
|
21(70.0%)
|
History of gastrectomy
|
YES
|
20(66.7%)
|
NO
|
10(33.3%)
|
Table 1. Baseline demographic and patient characteristics. ECOG Eastern Cooperative Oncology group, GC gastric, GEJ gastroesophageal junction tumors, MSI microsatellite instability, dMMR deficient mismatch repair, MSS microsatellite stability, MSI-H high microsatellite instability, EBER Epstein-Barr encoding region.
(66.7%) patients were negative; and 7 (23.3%) patients were unknown. PD-L1 expression was positive in 2 cases (6.7%); negative in 6 cases (20.0%); unknown in 22
cases (73.3%). 12 patients (40.0%) with MSS type; 1 patient (3.3%) with MSI-H type; unknown in 17 (56.7%). Due to the limitations of detection reagents, PD-L1, MMR and EBER are not the routine detection standards of the pathology department of our hospital. As well as the economic problems of patients, a large number of patients have not been tested.
Clinical Efficacy
Two patients (6.7%) achieved PR, 22 patients (73.3%) had SD, 6 patients (20.0%) had PD, and no patients (0.0%) achieved CR. Meanwhile, the ORR and DCR were 6.7% and 80.0%, respectively (Table 2).
The mPFS of the patients was 3.7 months (95% CI=2.5-5.0) and the mOS was 13.6 months (95% CI=9.7 – 17.6) (Figure 1A, B). We further analyzed the relationship between some factors and the therapeutic effect. Compared with the patients with GC and GEJ, the mPFS were 4.2 months (95% CI=0.4-8.0) and 3.7 months (95% CI=1.2-6.3) (p=0.544), respectively (Figure 2A). The mPFS of patients who had previously undergone gastrectomy and those who had not undergone gastrectomy was 4.4 months (95% CI=1.5-7.2) and 3.1 months (95% CI=2.5-3.8) (p=0.228), respectively (Figure 2B). In addition, the mPFS of patients who had received immunotherapy before compared with those of patients who had not received immunotherapy was 3.7 months (95% CI =2.2-5.3) and 3.3 months (95% CI =0.6-6.0) (p=0.377), respectively (Figure 2C). The mPFS of patients without liver metastasis and patients with liver metastasis was 4.3 months (95% CI =1.8-6.7) and 3.5 months (95% CI =2.8-4.2) (p=0.812), respectively (Figure 2D). The results showed that these factors had no significant impact on PFS.
Table 2. Efficacy of sintilimab combined with targeted drugs in the treatment of advanced metastatic gastric cancer. CR complete response, PR partial response, SD stable disease, PD progressive disease, ORR overall response rate, DCR disease control rate, GC Gastric, GEJ gastroesophageal junction tumors
Parameter
|
Response
|
ORR
|
DCR
|
|
CR
|
PR
|
SD
|
PD
|
|
Total
|
0
|
2
|
22
|
6
|
6.7%
|
80%
|
Previous immunotherapy
|
Yes
|
0
|
1
|
6
|
2
|
11.1%
|
77.8%
|
No
|
0
|
1
|
16
|
4
|
4.8%
|
81.0%
|
Previous gastrectomy
|
YES
|
0
|
2
|
13
|
5
|
6.7%
|
50.0%
|
NO
|
0
|
0
|
9
|
1
|
0
|
30.0%
|
Primary tumor site
|
GC
|
0
|
2
|
13
|
6
|
9.5%
|
71.4%
|
GEJ
|
0
|
0
|
9
|
0
|
0
|
100%
|
Liver metastasis
|
Yes
|
0
|
2
|
10
|
4
|
12.5%
|
75%
|
No
|
0
|
0
|
12
|
2
|
0
|
85.7%
|
Safety
The most common AEs included anemia (53.3%), fatigue (50.0%), leukopenia (26.7%), hypothyroidism (26.7%), nausea and vomiting (23.3%), thrombocytopenia (20.0%),
and neutropenia (20.0%). Meanwhile, grade 3 and above AEs included anemia (6.7%), neutropenia (6.7%) and leukopenia (6.7%), thrombocytopenia (3.3%), elevated aspartic aminotransferase (3.3%), and alanine aminotransferase (6.7%). The adverse reactions are basically controllable. No treatment-related deaths occurred (Table 3).
Table 3 . Treatment-Related Adverse Events.
Adverse event
|
Any grade, n(%)
|
Grades 1-2, n(%)
|
Grade ≥3, n(%)
|
Fatigue
|
15(50.0%)
|
15(50.0%)
|
0
|
Diarrhea
|
1(3.3%)
|
1(3.3%)
|
0
|
Nausea
|
4(13.3%)
|
4(13.3%)
|
0
|
Vomiting
|
3(10.0%)
|
3(10.0%)
|
0
|
Rash
|
1(3.3%)
|
1(3.3%)
|
0
|
Anemia
|
16(53.3%)
|
14(46.7%)
|
2(6.7%)
|
Hypothyroidism
|
8(26.7%)
|
8(26.7%)
|
0
|
Decreased neutrophil count
|
6(20.0%)
|
4(13.3%)
|
2(6.7%)
|
Decreased white blood count
|
8(26.7%)
|
6(20.0%)
|
2(6.7%)
|
Platelet count decreased
|
6(20.0%)
|
5(16.7%)
|
1(3.3%)
|
Increased aspartate aminotransferase
|
8(26.7%)
|
7(23.3%)
|
1(3.3%)
|
Increased alanine aminotransferase
|
7(23.3%)
|
5(16.7%)
|
2(6.7%)
|
Myocardial enzyme elevation
|
3(10.0%)
|
3(10.0%)
|
0
|
Hand-foot syndrome
|
2(6.7%)
|
2(6.7%)
|
0
|