Background In China, gastric cancer (GC) ranks second in incidence and mortality. Over 80% of patients with GC were diagnosed at an advanced stage with poor clinical outcome. Chemotherapy was the mainstream treatment with limited benefit. Apatinib, an inhibitor of targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for third-line treatment of advanced gastric cancer. However, the data of apatinib treatment in the real-world setting are limited. In this real-world study, we aimed to understand the current treatment pattern of apatinib, investigate the effectiveness and safety of apatinib in real-world settings, and explore the potential factors associated with the clinical outcomes. Methods This was a prospective, multicenter observational study in a real-world setting. Patients aged ≥18 years with histologic diagnosis of advanced GC were eligible for enrollment. The eligible patients received either apatinib monotherapy or apatinib plus chemotherapy by physician’s discretion. Apatinib treatment could be used as first-line, second-line, or third-line and above therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), ORR, DCR, and safety profile. Results A total of 737 patients with advanced gastric cancer treated with apatinib were included in the FAS population. A total of 54.9% patients used apatinib monotherapy and 45.1% patients used apatinib combination therapy. A total of 44.1% patients received apatinib in first-line treatment, 28.2% in second-line, and 27.7% in third-line and above. In first-line treatment, the objective response rate (ORR) was 9.09% and 16.42% in apatinib monotherapy and combination therapy groups, and disease control rate (DCR) was 78.41% and 89.29%, respectively. Patients who received combination therapy achieved significantly longer median progression-free survival (mPFS; 6.18 vs 3.52 months, p <0.01) and median overall survival (mOS; 8.72 vs 5.92 months, p <0.01) compared with monotherapy. In second-line and third-line therapy, combination therapy showed a better trend in tumor response and survival outcomes compared with monotherapy. For all patients, apatinib combined with paclitaxel were associated with longer mPFS compared with other combinations (8.88 vs 6.62 months). Multivariate analysis showed that combination with paclitaxel ( p =0.02) and experience of apatinib-related specific AEs ( p <0.01) were independent predictors for PFS and OS. The safety profile was tolerable and no unexpected adverse events were reported. Conclusion In a real-world setting, apatinib showed a favorable effectiveness and safety profile in patients with advanced gastric cancer. Apatinib combination therapy, especially combined with paclitaxel, might lead to better survival benefit in first-line treat...
Apatinib has been demonstrated to be effective and safe among patients with gastric cancer failing after at least two lines chemotherapy. This study aimed to evaluate its effectiveness and safety of low‐dose apatinib for the treatment of gastric cancer in real‐world practice. We performed a prospective, multicenter observation study in a real‐world setting. Patients with advanced gastric cancer more than 18 years old were eligible and received low‐dose apatinib (500 mg or 250mg per day) therapy. The median progression‐free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Between September 2017 and April 2019, a total of 747 patients were enrolled. The mPFS was 5.56 months (95% CI 4.47‐6.28), and mOS was 7.5 months (95% CI 6.74‐8.88). Four patients achieved complete response, 47 achieved partial response, and 374 patients achieved stable disease. The ORR was 6.83% and DCR was 56.89%. In addition, multivariate Cox regression analysis indicated that hand‐foot syndrome was one independent predictor for PFS and OS. The most common adverse events (AEs) at any grade were hypertension (36.55%), proteinuria (10.26%), hand‐foot syndrome (33.53%), fatigue (24.9%), anemia (57.35%), leukopenia (44.49%), thrombocytopenia (34.21%), and neutropenia (53.33%). Grade 3‐4 AEs with incidences of 5% or greater were anemia (13.97%), thrombocytopenia (7.14%), and neutropenia (6.67%). No treatment‐related death was observed during the treatment of apatinib. The prospective study suggested that low‐dose apatinib was an effective regimen for the treatment of advanced gastric cancer with tolerable or controlled toxicity in real world. Trial registration: NCT03333967.
Tissue-resident macrophages are highly heterogenous and perform various dedicated functions depending on their locations. In particular, skin resident macrophages have intriguing roles in long-distance intercellular signaling by mediating cellular protrusions called 'airinemes' in zebrafish. During pigment pattern formation, macrophages relay signaling molecules containing 'airineme vesicles' from one pigment cell to another. Without macrophages, airineme-mediated signaling is abolished, disrupting pigment pattern formation. It remains unknown, however, if the same macrophage population controls both these signaling roles and typical immune functions or if a separate macrophage subpopulation functions in intercellular communication. In this study, with high-resolution confocal live-imaging and cell type-specific genetic ablation approaches in vivo, we have identified a macrophage subpopulation responsible for airineme-mediated signaling. These cells appear distinct from conventional skin resident macrophages by their amoeboid morphology and faster/expansive migratory behaviors. Instead, we show that they resemble ectoderm-derived macrophages termed metaphocytes. Metaphocyte ablation dramatically reduces airineme extension and signaling. In addition, these amoeboid/metaphocytes require high levels of MMP9 expression for their migration and airineme-mediated signaling. These results reveal a novel macrophage subpopulation with specialized functions in airineme-mediated signaling, which may play roles in many other aspects of intercellular communication.
Page 6980, Effectiveness, second paragraph, last sentence, the text "In third-line and above, the DCR was 81.82% vs 76.59% with no significant difference between the two treatment groups (Table 2)" should read "In third-line and above, the DCR was 74.23% vs 81.82% with no significant difference between the two treatment groups (Table 2)".The data in Table 2 on page 6980 is incorrect. The correct Table 2 is shown below.The authors apologize for these errors and advise they do not affect the results of the paper.
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