Perioperative camrelizumab and apatinib combined with chemotherapy for locally advanced gastric cancer in China: three-year survival outcomes of phase 2 randomized controlled trial.

Background: The Arise-FJ-G005 study compared the efficacy and safety of perioperative camrelizumab and apatinib combined with chemotherapy with those of perioperative chemotherapy alone for locally advanced gastric cancer (LAGC) and assessed its effect on major pathological response (MPR). Herein, we report the 3-year survival outcomes of this trial. Methods: Arise-FJ-G005 was a multicenter, open-label, phase 2, randomized controlled trial (NCT04195828), conducted between June 2020 and March 2022. Patients with LAGC (clinical T2-4, N+, M0) were randomly assigned to receive perioperative CA-SAP (camrelizumab and apatinib combined with nab-paclitaxel plus S-1 [SAP]) or SAP alone for three cycles preoperatively and five cycles postoperatively. The primary endpoint was the MPR. This report focuses on the secondary endpoints of 3-year progression-free survival (PFS) and overall survival (OS). Findings: Between June 18, 2020, and March 31, 2022, 106 patients were randomly assigned to the CA-SAP or the SAP group in a 1:1 ratio, of whom 51 in the CA-SAP and 53 in the SAP group were included in the modified intention-to-treat analysis. The 3-year PFS was 64% (95% confidence [CI]: 52%-79%) and 48% (95% CI: 36%-64%) in the CA-SAP and SAP groups, respectively, with an adjusted hazard ratio (HR) of 0.512 (95% CI: 0.263-0.998). The 3-year OS was 63% (95% CI: 51%-78%) and 61% (95% CI: 49%-77%) in the CA-SAP and SAP groups, respectively (adjusted HR: 0.987, 95% CI: 0.481-2.026). Exploratory analysis revealed heterogeneity in the treatment effect among subgroups according to performance status. Interpretation: Adding camrelizumab and apatinib to perioperative chemotherapy did not result in a meaningful improvement in the 3-year OS of unselected patients with LAGC. Due to its suboptimal tolerability and effectiveness, future research should focus on identifying subpopulations that may benefit from this combination treatment strategy. Funding: Construction Funds for "High-level Hospitals and Clinical Specialties" of Fujian Province (No. [2021]76).