Combining immune checkpoint inhibitors with standard treatment regimens in advanced human epidermal growth factor receptor-2 positive gastric cancer patients

Abstract

BACKGROUND

Gastric cancer is one of the most common malignant tumors worldwide, with its incidence and mortality rates ranking among the highest in gastrointestinal cancers. The overexpression or gene amplification of human epidermal growth factor receptor 2 (HER-2) occurs in approximately 15%-20% of gastric cancers and serves as a critical molecular target influencing prognosis and treatment outcomes. For patients with HER-2-positive gastric cancer, trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment. However, despite the demonstrated clinical benefits in prolonging survival, the overall efficacy remains limited. In recent years, with the successful application of immune checkpoint inhibitors (ICIs) in various malignant tumors, combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer. Nevertheless, the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.

AIM

To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.

METHODS

Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed. Patients were divided into a control group (n = 54, treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen) and an observation group (n = 50, treated with ICIs in addition to the standard regimen). The therapeutic efficacy, survival outcomes, and adverse reactions were compared between the two groups. Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.

RESULTS

With a median follow-up time of 14.6 months, there were no significant differences between the two groups in terms of objective response rate or disease control rate (P > 0.05). The median progression-free survival (mPFS) and mPFS for patients with immunohistochemistry 3 + in the observation group were significantly higher than those in the control group (P < 0.05). Among patients in the observation group, those with positive programmed death-ligand 1 (PD-L1) expression had a significantly higher mPFS than those with negative PD-L1 expression (P < 0.05). Regarding adverse events, significant differences were observed between the two groups in hypothyroidism and neutropenia (P < 0.05). Cox multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status, peritoneal metastasis, positive programmed death-1 expression, and treatment regimen were independent factors influencing PFS (hazard ratio > 1, P < 0.05).

CONCLUSION

ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy, significantly prolonging PFS with manageable safety. ECOG performance status, peritoneal metastasis, positive PD-L1 expression, and treatment regimen are independent factors influencing PFS, warranting increased clinical attention to patients exhibiting these factors.

Keywords: Advanced; Human epidermal growth factor receptor 2-positive; Gastric cancer; Standard treatment regimen; Immune checkpoint inhibitors; Efficacy; Safety; Prognosis; Influencing factors

Core Tip: Immune checkpoint inhibitors combined with standard treatment regimens for patients with advanced human epidermal growth factor receptor 2-positive gastric cancer demonstrate favorable clinical efficacy, significantly prolonging progression-free survival with manageable safety. Eastern Cooperative Oncology Group performance status, peritoneal metastasis, positive programmed death-ligand 1 expression, and treatment regimen are independent factors influencing progression-free survival, warranting increased clinical attention to patients exhibiting these factors.