Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS‐mutant metastatic colorectal cancer

et al. 2023

Aging

Background: CLDN5 protein is essential for the formation of tight junctions in epithelial cells, and has been associated with epithelial-mesenchymal transition. Research has indicated that CLDN5 is associated with tumor metastasis, the tumor microenvironment, and immunotherapy in multiple types of cancer. Also, no comprehensive evaluation of the expression of CLDN5 and immunotherapy signatures through a pan-cancer analysis or immunoassay has been performed. Methods: We explored CLDN5's differential expression, survival analysis and clinicopathological staging through the TCGA database, and then corroborated the expression of CLDN5 by utilizing the GEO (Gene expression omnibus) database. To analyze CLDN5 KEGG, GO, and Hallmark mutations, as well as TIMER for immune infiltration, GSEA was utilized with ROC curve, mutation, and other factors such as survival, pathological stage, TME, MSI, TMB, immune cell infiltration, and DNA methylation. Immunohistochemistry was used to assess CLDN5 staining in gastric cancer tissues and paracancerous tissues. Visualization was done with R version 4.2.0 ( http://www.rproject.org/ ). Results: According to TCGA database, CLDN5 expression levels differed significantly between cancer and normal tissues, and the GEO database (GSE49051 and GSE 64951) and tissue microarrays confirmed this result. Infiltrating cluster of differentiation 8+ (CD8+) T cells, CD4+ cells, neutrophils, dendritic cells, and macrophages revealed a correlation with CLDN5 expression. DNA methylation, TMB, and MSI are related to CLDN5 expression. Based on the ROC curve analysis, CLDN5 demonstrates outstanding diagnostic effectiveness for gastric cancer and is comparable to CA-199. Conclusions: The findings suggest that CLDN5 is implicated in the oncogenesis of diverse cancer types, underscoring its potential significance in cancer biology. Notably, CLDN5 could have implications in immune filtration and immune checkpoint inhibitor therapies, however, further research is needed to confirm this.

Section: Discussionmentioning

confidence: 99%

CLDN5 identified as a biomarker for metastasis and immune infiltration in gastric cancer via pan-cancer analysis

Han

Cui

et al. 2023

Aging

“…Some combination strategies have shown benefits as well. There is a retrospective study comparing bevacizumab plus capecitabine, with capecitabine monotherapy for KRAS-mutant metastatic CRC showing that combination therapy was better tolerated, and also contributing a longer PFS (9.0 months vs. 7.2 months, p < 0.05) [ 82 ]. Another study found that conventional mFOLFOX6 chemotherapy combined with cetuximab for KRAS-mutant CRC patients showed was shown to improve efficacy, reduce the overall incidence of adverse events (AEs), improve OS, and extend overall patient survival when adding simvastatin [ 83 ].…”

Section: Therapeutic Strategies In Kras-mutant Cancersmentioning

confidence: 99%

KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration

Yang

Zhang

et al. 2023

JCM

Kristen rat sarcoma (KRAS) gene is one of the most common mutated oncogenes in solid tumors. Yet, KRAS inhibitors did not follow suit with the development of targeted therapy, for the structure of KRAS has been considered as being implausible to target for decades. Chemotherapy was the initial recommended therapy for KRAS-mutant cancer patients, which was then replaced by or combined with immunotherapy. KRAS G12C inhibitors became the most recent breakthrough in targeted therapy, with Sotorasib being approved by the Food and Drug Administration (FDA) based on its significant efficacy in multiple clinical studies. However, the subtypes of the KRAS mutations are complex, and the development of inhibitors targeting non-G12C subtypes is still at a relatively early stage. In addition, the monotherapy of KRAS inhibitors has accumulated possible resistance, acquiring the exploration of combination therapies or next-generation KRAS inhibitors. Thus, other non-target, conventional therapies have also been considered as being promising. Here in this review, we went through the characteristics of KRAS mutations in cancer patients, and the prognostic effect that it poses on different therapies and advanced therapeutic strategy, as well as cutting-edge research on the mechanisms of drug resistance, tumor development, and the immune microenvironment.

Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS‐mutant metastatic colorectal cancer

Clinical Pharmacy Therapeu

Zhang

Tian

et al. 2022

Self Cite

What is known and objectives The optimal strategy for maintenance therapy in patients with metastatic colorectal cancer (mCRC) remains controversial. Considering that, beyond progression, co‐therapy with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate. We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS‐mutant mCRC （as defined by mutations in KRAS and NRAS exons 2–4）controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks. Methods We retrospectively analysed patients with RAS‐mutant mCRC admitted to the Department of Oncology, Huizhou Municipal Central Hospital from December, 2015 to December, 2020. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 154 patients whose disease was brought under control then continued maintenance therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The efficacy and adverse effects of maintenance treatment were compared between the two groups. The clinicopathological characteristics such as sex, age, performance status (PS) score, primary tumour site, degree of pathological differentiation, baseline carcinoembryonic antigen (CEA) level, microsatellite instability (MSI) status, number of metastatic tumour sites and efficacy of induction treatment were compared in terms of prognosis. Results and discussion The median progression‐free survival (mPFS)of patients was 9.0 months (95% CI 8.0–10.0) in the observation group and 7.2 months (95% CI 6.0–8.4) in the control group, with a statistically significant difference (p < 0.05). The baseline CEA level was an independent prognostic factor. Both groups tolerated the toxic side effects. What is new and conclusion Bevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone, and it is worthy of popularization in clinical practice.