4.1 Literature search results
52 literatures were preliminarily retrieved, and 12 studies were finally included after case reports, duplicate literatures, reviews, retrospective studies, non-randomized studies, before-and-after control studies or studies that did not meet the inclusion criteria were excluded. The specific screening process is shown in Figure 1. Table 1 shows the detailed information of the 12 literatures included in this study.
Table 1. Basic characteristics of the included literature
Included literature
|
Number of samples Experimental\Control group
|
Indicators
|
Wu Lili 2019 [11]
|
30
|
30
|
CR, PR, SD, PD, ORR, Nausea, Myelosuppression, Hypertension, Albuminuria
|
Bai Dewei 2023 [12]
|
42
|
42
|
CR, PR, SD, PD, ORR, Nausea, Myelosuppression, Hypertension, Albuminuria, CEA, CA199
|
LI Jing 2018 [13]
|
18
|
29
|
CR, PR, SD, PD, ORR, Nausea, Hypertension, Albuminuria
|
Wang Jianping 2023 [14]
|
32
|
32
|
CR, PR, SD, PD, ORR, Myelosuppression, Hypertension, Albuminuria, CEA, CA199
|
FANG Lilan 2022 [15]
|
30
|
30
|
CR, PR, SD, PD, ORR, Nausea, Myelosuppression, Hypertension, CEA, CA199
|
WU Wei-xia 2020 [16]
|
18
|
17
|
CR, PR, SD, PD, ORR, Nausea, Myelosuppression, Albuminuria, mPFS
|
Feng Yanfei 2020 [17]
|
48
|
48
|
CR, PR, SD, PD, ORR, Nausea, Myelosuppression, Hypertension, Albuminuria, CEA, CA199, mPFS, OS
|
LI Chu-yun 2020 [18]
|
24
|
24
|
CR, PR, SD, PD, ORR, Nausea, Albuminuria, CEA, CA199
|
YANG Zunjing 2019 [19]
|
31
|
31
|
ORR, Hypertension, mPFS, OS
|
Jin Li 2016 [20]
|
176
|
91
|
CR, PR, SD, PD, ORR, Nausea, Myelosuppression, Hypertension, Albuminuria, CEA, CA199, mPFS, OS
|
Sun Jifeng 2019 [21]
|
39
|
39
|
CR, PR, SD, PD, ORR, Nausea, Myelosuppressio
|
Ding Shugen 2021 [22]
|
52
|
52
|
CR, PR, SD, PD, ORR, CEA, CA199, mPFS, OS
|
4.2 The publication bias analysis
Further quality assessment was conducted on the 12 literatures included in this study, and the risk bias was shown in Figure 2. The results show that the overall quality of the 12 articles is high, the deviation is within the acceptable range, and meets the quality standard.
4.3 Meta analysis results
4.3.1 The sample number of the two groups of patients was analyzed
As shown in Figure 3 and 4, the total number of patients in the two groups participating in the study was counted. The results showed that 540 patients in the experimental group and 465 patients in the control group. The number of patients in the two groups was similar, and the difference was not statistically significant (95%CI (0.99,1.01), P=1.00).
4.3.2 The mean ages and the number of male patients in the two groups were similar
Patient age can affect disease progression, so the average age of patients with advanced gastric cancer was compared between the two groups. Results as shown in Figure 5 and Figure 6, most patients with advanced gastric cancer were over 45 years old, and there was no statistical significance between the two groups (95%CI (-1.84,0.64), P=0.34). The number of male patients in each group was compared, and the results were shown in Figure 7 and 8. The results showed that there was no significant gender difference between the two groups (95%CI (0.92,1.11), P=0.83).
4.3.3 The patients were at the same stage of the disease before treatment
CEA and CA199 are tumor markers, and monitoring their levels is helpful to evaluate the therapeutic effect of gastric cancer. Its CEA is an acidic glycoprotein. When gastric cancer occurs, the serum CEA level increases abnormally. CA199 is a gastrointestinal tumor-associated antigen in the blood circulation and a sensitive marker for malignant tumors of the digestive system. The levels of the two groups before treatment were compared, and the results were shown in Figure 11-14. The results showed no significant difference in CEA (95%CI (-0.30, 0.58), I2=0%, P=0.54) and CA199 (95%CI (-0.49, 0.41), I2=18%, P=0.85) levels between the two groups.
4.3.4 Apatinib can effectively relieve the disease in patients with advanced gastric cancer
CR indicates the disappearance of tumor lesions and remains for at least 4 weeks. PR reduced the maximum sum of single diameters of tumors by more than 30% and was maintained for at least 4 weeks. SD was less than 30% reduction in the sum of the largest single diameters of the tumor, or less than 20% increase in the sum of the largest single diameters of the tumor, with no new lesions. PD was the largest single diameter of the tumor and increased amplitude≥20%, or there were new lesions. The objective response rate was the sum of CR and PR. The differences in the above indexes between the two groups were compared, as shown in Figure 15-24. Apatinib can effectively increase CR (95%CI (1.49, 3.91), I2=0%, P=0.0004), PR (95%CI (1.49, 2.93), I2=0%, P<0.0001) and ORR (95%CI (2.27, 4.54), I2=0%, P<0.00001) and reduce PD (95%CI (0.22, 0.45), I2=0%, P<0.00001) in patients with advanced gastric cancer. It had no significant effect on SD (95%CI (0.72, 1.39), I2=0%, P=0.99).
4.3.5 Apatinib can effectively reduce tumor markers in patients with advanced gastric cancer
The differences of CEA and CA199 levels in patients after treatment were compared, and the results were shown in Figure 25-28. The results showed that Apatinib could effectively reduce the levels of CEA (95%CI (-9.35, -3.63), I2=98%, P<0.00001) and CA199 (95%CI (-11.20, -1.41), I2=100%, P=0.01) in patients with advanced gastric cancer, with statistical differences.
4.3.6 There was no significant difference in side effects between the two groups
Advanced gastric cancer patients suffer from pain, and the treatment process also produces side effects, such as nausea, myelosuppression, hypertension, albuminuria and so on. The difference of side effects between the two groups after treatment was compared, and the results were shown in Figure 29-36. The results showed that there were no significant differences between Apatinib and the control group in nausea (95%CI (0.54, 1.37), I2=0%, P=0.52), myelosuppression (95%CI (0.54, 1.68), I2=0%, P=0.87), hypertension (95%CI (0.98, 3.01), I2=4%, P=0.06), and albuminuria (95%CI (0.63, 1.83), I2=5%, P=0.80) in the treatment of advanced gastric cancer, so the side effects were negligible.
4.3.7 Apatinib prolongs mPFS and OS in patients with advanced gastric cancer
mPFS represents the time of survival at which half of the patients in the study had a specific event such as tumor progression. OS refers to the time from the date of randomization until the patient died from any cause. The differences in mPFS and OS between the two groups were compared, as shown in Figure 37-40. According to the results, Apatinib in the treatment of advanced gastric cancer can significantly prolong mPFS (95%CI (0.43, 1.63), I2=93%, P=0.0008) and OS (95%CI (0.22, 2.43), I2=97%, P=0.02) in patients.