Efficacy and prognostic factors of PD-1 inhibitors combined with apatinib in advanced diffuse gastric cancer

Beibei Chen, Huichen Zhao, Huihui Hu, Jinxi Huang, Yingjun Liu, Huifang Lv, Weifeng Xu, Jianzheng Wang, Caiyun Nie, Jing Zhao, Yunduan He, Saiqi Wang, Yuhang Wang,  Xiaobing Chen

Abstract:

Refractory diffuse gastric cancer (DGC) is rising in incidence and has a bad prognosis. Individuals who are administered second-line or subsequent therapies frequently exhibit diminished physical fitness, rendering them inappropriate for intensive treatment. Despite this, PD-1 inhibitors and anti-angiogenesis drug apatinib have demonstrated efficacy in advanced gastric cancer. This study aimed to evaluate the effectiveness, prognostic factors, and safety of PD-1 inhibitors in combination with apatinib in advanced DGC. The present study is a retrospective analysis of 34 patients with advanced DGC treated with apatinib combined with PD-1 inhibitors in the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2022. Apatinib 250 mg was administered to patients once a day. The median progression-free survival (mPFS) and the median overall survival (mOS) were estimated using Kaplan-Meier curves, whereas objective response rate (ORR), disease control rate (DCR), prognostic variables, and adverse events were among the other outcomes. Data from 34 patients were collected, and the ORR was 5.9% (2 out of 34), while the DCR was 55.9% (19 out of 34). The mPFS was 2.5 months (95% CI: 1.9–3.0), while the mOS was 6.8 months (95% CI: 3.7-9.9). Log-rank univariate analysis indicated that the mOS of patients with carcinoembryonic antigen (CEA) levels <4.7 ng/ml (11.3 months, 95% CI: 7.1–15.5) was significantly different from those with levels ≥4.7 ng/ml (2.7 months, 95% CI: 0.0–6.1) (p=0.008). A notable disparity in mOS and mPFS was observed between patients with CA125 <35 U/ml (7.7 months, 95% CI: 3.6–11.9) and those with CA125 ≥35 U/ml (2.5 months, 95% CI: 1.9–3.0) (p=0.003), as well as between patients with lactate dehydrogenase (LDH) <245 U/l (11.3 months, 95% CI: 7.2–15.5) and those with LDH ≥245 U/l (2.2 months, 95% CI: 1.5–2.9) (p=0.007), and between patients with PLTs <350×10(exp9)/l (7.5 months, 95% CI: 6.4–8.7) compared to those with PLTs ≥350×10(exp9)/l (1.7 months, 95% CI: 0.0–3.9) (p=0.001). Multivariate Cox regression analysis indicated that CA125, LDH, and PLT levels were independent prognostic variables. The occurrence of grade 3 or 4 treatment-related adverse events was 17.6% (6/34). The study suggests that the integration of PD-1 inhibitors and apatinib in second-line and subsequent therapies demonstrated promising efficacy and acceptable safety in advanced DGC patients. The concentrations of CA125, LDH, and PLTs may serve as prognostic indicators for DGC.