1. Introduction

Gastric cancer is a highly prevalent and deadly malignant tumor that poses a significant threat to human health [1]. It is currently the third most common cancer globally, has a high clinical mortality rate, can take on various forms morphologically, and has an age-related specificity, with the risk of developing the disease increasing after age 40 and peaking at age 75. While some regions have seen a decline in gastric cancer incidence, the disease still accounts for over 1 million new cases and 78,400 deaths worldwide annually. Lower rates of gastric cancer and mortality have been linked to various factors, such as reduced consumption of salted, pickled, smoked, and chemically preserved foods that contain nitrates and increased intake of fresh fruits and vegetables. Gastric cancer is more common in males and may be due to factors such as smoking, occupational stress, eating disorders, or hormonal imbalances. Therefore, it is crucial to take these risk factors into account when considering preventative measures and treatment options for gastric cancer.

Gastric cancer often presents with subtle symptoms, making it difficult to detect in its early stages. Consequently, a significant number of patients are diagnosed during the middle or advanced stages, leading to a poor clinical prognosis [2, 3]. Previous clinical experience has demonstrated [4, 5] that chemotherapy should remain the primary treatment for advanced gastric cancer, as other therapies have exhibited limited clinical effectiveness. Although surgery is typically an essential component of treatment, offering the best opportunity for long-term survival, it may not be feasible for patients who cannot tolerate it or those with extensively spread cancer, whereby alternative treatments, including chemotherapy and radiation therapy, can be employed instead of surgery.

Patients with poor response to first-line chemotherapy may be considered for second-line chemotherapy, which can show significant differences in clinical efficacy [6]. However, delayed subsequent treatment can limit the effectiveness of other treatment options, emphasizing the need for research on third-line chemotherapy regimens for advanced gastric cancer [7, 8]. With the continuous advancement of medical technology, multi-target inhibitors have emerged as advantageous in the clinical treatment of advanced cancer, particularly in inhibiting angiogenic antibodies. In line with the therapeutic concept of combining anti-angiogenesis targeted inhibitors with PD-1 inhibitors, our hospital has actively summarized clinical experience and applied a treatment regimen of anlotinib combined with camrelizumab for male patients with advanced gastric cancer. The synergistic effect of the two drugs was shown to effectively reduce the invasion and migration of tumor cells while enhancing their killing effect. Overall, the use of anlotinib integrated with camrelizumab has been found to be effective in controlling tumor progression, improving clinical efficacy and prolonging patient survival without an increase in adverse reactions. Herein, we performed a comparative study on its clinical efficacy in male patients with gastric cancer.

2. Materials and methods

3. Results

4. Discussion

Advanced gastric cancer patients who fail to respond to first-line therapy face a high risk of relapse, progression, and ultimately, increased mortality rates [9]. In such cases, personalized second-line treatments are administered based on prior clinical practice and patient tolerance. However, the effectiveness of these treatments varies significantly due to differences in individual patient conditions [10], with some patients not experiencing any notable improvements in survival. Currently, there is a lack of clear criteria and clinical study data for third-line treatment options for advanced gastric cancer. Nevertheless, the ongoing advancement of medical technology has led to the development of multi-target inhibitors, particularly anti-angiogenic antibodies [11], which have shown promise in treating advanced cancer and gained increasing attention in clinical practice, demonstrating potential advantages for managing advanced gastric cancer.

Immune escape, a crucial mechanism in the formation and progression of malignant tumors, has become a vital focus in clinical research [12]. Studies have found [13, 14] that PD-1 acts as an innate inhibitor of immune responses, suppressing T cell activity and impairing T cell function, ultimately reducing their effectiveness against tumors. By inhibiting PD-1, T cell activity can be improved, bolstering their ability to combat tumors. This principle underpins the effectiveness of PD-1 inhibitors in treating advanced solid malignancies [15, 16, 17].

The indole group of anlotinib has been found to effectively inhibit Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and Vascular Endothelial Growth Factor Receptor 3 (VEGFR3), thereby preventing the formation of tumor vasculature and lymphatic vasculature and suppressing tumor metastasis [18, 19]. Relevant clinical data [20, 21] has indicated that the objective response rate and disease control rate of patients with advanced lung adenocarcinoma resistant to previous treatment could reach more than 40% and 80%, respectively, when treated with anlotinib. However, in the clinical practice of advanced non-small cell lung cancer, the above two indicators were only about 7% and 67%, respectively.

PD-1 inhibitors are among the most widely studied immune-targeted drugs in clinical research [22, 23]. As of September 2021, China has approved eight such drugs, including nivolumab and camrelizumab. Nivolumab was the first PD-1 inhibitor approved for gastric cancer treatment in China, significantly addressing the limitations of later-line therapies for this disease. However, its high treatment cost restricts its clinical application [24, 25]. Conversely, camrelizumab is a PD-1 inhibitor developed independently in China. Clinical studies have demonstrated its effectiveness in prolonging overall survival for patients with various tumor types compared to conventional chemotherapy. Additionally, camrelizumab exhibits the lowest toxicity among immune-targeted agents when used in second- or third-line treatment regimens [26, 27].

Based on treatment strategies of combining anti-angiogenesis targeted inhibitors with PD-1 inhibitors, this approach is implemented in our hospital for the clinical treatment of male patients with advanced gastric cancer and achieved good clinical results. The results of this study demonstrated that in terms of clinical efficacy, Group B had significantly higher ORR and DCR than Group A. After treatment, the treatment efficacies in Group B were also superior to Group A, particularly in terms of PD-1 from VEGF, CD4+ T cells, CD8+ T cells, immune function indicators and tumor markers such as CA50, CEA and CYFRA21-1. Progression-free survival and overall survival were also significantly longer in Group B compared to Group A, and the incidence of adverse reactions in Group B, despite using combination therapy, was similar to that of Group A. Thus, the combination of anlotinib and camrelizumab could be used to achieve greater clinical effectiveness for treating advanced gastric cancer in males compared to anlotinib alone, which is consistent with previous reports [28].

In-depth studies discovered [29, 30] that the combination of the two drugs not only exerts the anti-angiogenic effect of tyrosine kinase inhibitors but also has the potential to enhance immune function like PD-1 inhibitors, thereby effectively reducing the invasion and migration ability of tumor tissues and cells while enhancing their killing effect.

5. Conclusions

In conclusion, the combination of anlotinib and camrelizumab demonstrated significant benefits in controlling tumor progression, improving clinical efficacy, and prolonging patient survival without increasing adverse reactions in male patients with advanced gastric cancer. Considering that this present study was limited by the predominantly male patient population and relatively small sample size and relatively short post-treatment follow-up time, further studies with larger sample sizes and longer follow-up periods are necessary to validate the clinical effectiveness of this treatment regimen.

Availability of Data and Materials

The authors declare that all data supporting the findings of this study are available within the paper, and any raw data can be obtained from the corresponding author upon request.

Author contributions

TLX—designed and performed the study; TLX, YSC, YPW, RG, JH and QDD—supervised the data collection, analyzed the data, interpreted the data, prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

Ethics approval and consent to participate

Ethical approval was obtained from the Ethics Committee of the People’s Hospital of Susong County (Approval no. 2019029). Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

Supplementary material associated with this article can be found, in the online version, at https://oss.jomh.org/files/article/1663426736407101440/attachment/Supplementary%20material.docx.