First-line Apatinib Combined With Tislelizumab and Chemotherapy for Advanced Gastric and Gastroesophageal Junction Adenocarcinoma Patients with Poor Prognosis.

Abstract

In this prospective, open-label, exploratory study (RENMIN-213), patients with previously untreated, HER2-negative, advanced G/GEJ adenocarcinoma patients with signet ring cell carcinoma or peritoneal metastasis, were enrolled to receive 8 cycles of apatinib, tislelizumab, and chemotherapy every 3 weeks, with a maintenance therapy with apatinib plus tislelizumab for a maximum of 1 year. Homogeneous patients receiving ICIs combined with chemotherapy at the same time were deemed as the control group for efficacy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), biomarkers, health-related quality of life (HRQoL), and safety. A total of 33 patients (median [range] age, 60 [32-72] years; 21 [63.6%] male; 11 [33.3%] signet ring cell carcinoma; 30 [90.9%] peritoneal metastasis) were enrolled and deemed evaluable for efficacy analysis. Of these patients, 32 (97%) were without progression disease, of whom one (3.0%) patient had complete response and 18 (54.6%) had partial response. 6 patients (18.2%) were able to undergo surgery after treatment. After propensity score matching, the median PFS was 10.17 months (95% CI: 7.13-13.21) of apatinib combined with tislelizumab and chemotherapy group, as compared with 6.0 months in ICIs combined with chemotherapy group. The median DOR increased from 4.5 months to 8.7months. ORR increased from 33.3% to 54.6% and DCR increased from 87.9% to 97.0%. Treatment-related grade 3 or higher adverse events for evaluable patients occurred in 11 patients (33.3%), patients' HRQoL improved after treatment.