Efficacy of everolimus combined with endocrine therapy in HR-positive/HER-2-negativeadvanced breast cancer.

PURPOSE: To explore the efficacy and safety of everolimus combined with endocrine therapy in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER-2)-negative advanced breast cancer. METHODS: The clinical information of 108 patients with HR-positive/HER-2-negative advanced breast cancer, who were admitted to and treated in our hospital from June 2014 to June 2016, was retrospectively analyzed. Of them, 54 patients were treated with everolimus combined with endocrine drugs (Everolimus group), while the other 54 patients underwent endocrine monotherapy (Control group). The clinical response rate and incidence of adverse reactions were compared between the two groups of patients, and the patients were followed up to record survival. Besides, the possible influencing factors for progression-free survival (PFS) were analyzed. RESULTS: The objective response rate (ORR) was 22.2% and 14.8%, respectively, in everolimus group and the Control group, while the clinical benefit rate (CBR) was 66.7% and 37.0%, respectively, in the two groups. There were statistically significant differences in the CBRs of the first-line and second-line therapies. The majority of adverse reactions were in grade I and II, with lower incidence rates of grade III and IV adverse reactions. The median PFS of the two groups of patients was 7.3±5.6 months and 6.7±5.1 months, respectively. The log-rank test revealed that there was a statistically significant difference in the PFS between the two groups of patients. According to the multivariate regression analysis results, progesterone receptor (PR)+, absence of visceral metastases, and sensitivity to endocrine therapy were the protective prognostic factors for PFS. CONCLUSION: Everolimus combined with endocrine therapy has significant clinical efficacy in patients with HR-positive/HER-2-negative advanced breast cancer, and can effectively improve the survival of patients with tolerable adverse reactions. PR+, absence of visceral metastases and sensitivity to endocrine therapy are the protective prognostic factors for PFS.

Targeting cluster of differentiation 47 improves the efficacy of anti-cytotoxic T-lymphocyte associated protein 4 treatment via antigen presentation enhancement in pancreatic ductal adenocarcinoma.

Treatment with cluster of differentiation 47 (CD47) monoclonal antibody has exhibited promising antitumor effects in various preclinical cancer models. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the present study, the CD47 expression level was measured in PDAC patient samples. The effects of CD47 on antigen presentation and anti-tumor immunity were evaluated using phagocytotic assays and animal models. The results indicated that CD47 was overexpressed in the tumor tissue of PDAC patients compared with that in normal adjacent tissues. In the human samples, antigen-presenting cells (macrophages and dendritic cells) in tumors with high CD47 expression demonstrated low CD80 and CD86 expression levels. In an in vitro co-culture tumor cell system, CD47 overexpression was observed to inhibit the function of phagocytic cells. Furthermore, in a PDAC mouse model, CD47 overexpression was indicated to reduce antigen-presenting cell tumor infiltration and T-cell priming in tumor-draining lymph nodes. Anti-CD47 treatment appeared to enhance the efficacy of the approved immune checkpoint blockade agent anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA4) in suppressing PDAC development in a mouse model. Therefore, it was concluded that CD47 overexpression suppressed antigen presentation and T-cell priming in PDAC. Anti-CD47 treatment may enhance the efficacy of anti-CTLA4 therapy and may therefore be a potential strategy for the treatment of PDAC patients in the future.