Abstract:

Background and purpose: There is a consensus within the medical community regarding the perioperative treatment of locally advanced gastric cancer (LAGC), yet the selection of an efficient and safe treatment strategy remains a contentious issue. Previous studies have validated the effectiveness of chemotherapy in conjunction with immune checkpoint inhibitor (ICI) and anti-angiogenic agents in the perioperative treatment of LAGC. This study aimed to investigate the perioperative treatment regimen combining ICI, anti-angiogenic drugs and chemotherapy, in order to provide additional references for the selection of perioperative treatment strategies for patients with LAGC. Methods: This was a prospective, single-arm exploratory study designed to assess the efficacy and safety of perioperative treatment with penpulimab combined with anlotinib and chemotherapy for potentially resectable stage T3-4N+M0 LAGC. Patients diagnosed with LAGC at the Inner Mongolia Autonomous Region People’s Hospital from January 2022 to December 2023 were enrolled in the study. The primary endpoints were pathological complete response (pCR) rate and major pathological remission (MPR) rate, while secondary endpoints included surgical conversion rate, objective response rate (ORR), disease-free survival (DFS), progression-free survival (PFS) and adverse reactions. Quality of life before and after treatment was evaluated using the European Organization for Research on Treatment of Cancer (EORTC) QLQ-STO22 Chinese version questionnaire. This study was reviewed and approved by the Ethics Committee of Inner Mongolia Autonomous Region People’s Hospital (number: 202404604L). Results: A total of 32 patients participated in the study, with an ORR of 78.1% (25/32). Of these, 18 patients underwent surgical treatment, achieving a pCR rate of 22.2% (4/18) and a MPR rate of 38.9% (7/18). The median PFS for patients who did not undergo surgery was 9.8 months (95% CI: 7.6-13.1), and the median follow-up duration was 16.4 months (95% CI: 11.7-22.5). For patients who received radical surgical resection, the median DFS was not reached, and the 1-year DFS rate was 88.8% (16/18). Common adverse reactions following the treatment included myelosuppression, liver function abnormalities, diarrhea and neurotoxicity, with most adverse events being grade 1-2, a few grade 3 adverse events, and no grade 4 or 5 adverse events. According to the EORTC QLQ-STO22 Chinese version questionnaire, significant improvements were observed in the domains of difficulty swallowing, pain and eating restrictions. Additionally, improvements were noted in anxiety and reflux symptoms, while changes in body image were less pronounced. Conclusion: In the perioperative treatment of LAGC, the combination therapy of oxaliplatin, tegafur, anlotinib and penpulimab can improve the efficacy while ensuring safety, and is expected to become a new treatment for LAGC.

Key words: Locally advanced gastric cancer, Perioperative treatment, Immunotherapy, Anti-angiogenic therapy, Efficacy evaluation, Quality of life assessment