Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development

Abstract Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers

Clinicopathologic characteristics, laboratory parameters, treatment protocols, and outcomes of pancreatic cancer: a retrospective cohort study of 1433 patients in China

Objectives The prognosis of people with pancreatic cancer is extremely unfavorable. However, the prognostic factors remain largely undefined. We aimed to perform comprehensive analyses of clinicopathologic characteristics, laboratory parameters, and treatment protocols for exploring their role as prognostic factors of pancreatic cancer. Methods Patients diagnosed with pancreatic cancer and hospitalized at the China National Cancer Center between April 2006 and May 2016 were enrolled in this retrospective cohort study. Clinicopathologic characteristics, laboratory parameters, and treatment protocols were compared among patients at different stages of the disease. The association between these factors and overall survival (OS) was analyzed using the Kaplan–Meier method and Cox proportional hazards model. Results The present study included 1,433 consecutive patients with pancreatic cancer. Median OS was 10.6 months (95% confidence interval [CI] 9.8–11.3 months), with 1-, 3-, and 5-year survival rates of 43.7%, 14.8%, and 8.8%, respectively. Cox multivariate analysis findings identified the following factors as independent predictors of OS: gender (female vs male, hazard ratio 0.72, 95% CI [0.54–0.95]); elevated total bilirubin (TBil; 1.82, 1.34–2.47); elevated carbohydrate antigen 19-9 (CA19-9; 1.72, 1.17–2.54); tumor being located in pancreatic body and tail (1.52, 1.10–2.10); advanced T stage (T3-4 vs T1-2, 1.62, 1.15–2.27); lymph node metastasis (1.57, 1.20–2.07); distant metastasis (1.59, 1.12–2.27); the presence of surgical resection (0.53, 0.34–0.81); and the presence of systemic chemotherapy (0.62, 0.45–0.82). Conclusions Being male, elevated TBil and carcinoembryonic antigen, tumor being located in pancreatic body and tail, advanced T stage, lymph node and distant metastasis, the absence of surgical resection, and the absence of systematic chemotherapy were associated with worse OS in patients with pancreatic cancer

Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China

Abstract Background Real-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China. Methods HR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test. Results In total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P < 0.05). The most common grade 3 or 4 adverse events (AE) was neutropenia (36.5%), and the most common nonhematologic AE was fatigue (10.9%). No patient experienced AE leading to treatment discontinuation. Conclusion Palbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 − MBC

Elevated expression of TUBA1C in breast cancer predicts poor prognosis.

α1C-tubulin (TUBA1C) is a member of the α-tubulin family and has served as a potential biomarker in a variety of cancers in many studies. In this study, the gene expression profile of TUBA1C in The Cancer Genome Atlas (TCGA) was extracted for analysis, and the prognostic value of TUBA1C in breast cancer was comprehensively evaluated. The Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression analysis were performed to confirm the correlations between TUBA1C expression and the clinical characteristics of breast cancer patients. The effect of TUBA1C expression on the survival of breast cancer patients was assessed by Kaplan-Meier curve, Cox regression analysis, and the Kaplan-Meier plotter (an online database). The TCGA data set was used for the Gene Set Enrichment Analysis (GSEA). The results confirmed that high TUBA1C expression in breast cancer was closely correlated with survival time, survival status, and tumor size. In addition, elevated TUBA1C expression can predict poor overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Univariate and multivariate analyses (Cox regression analyses) confirmed that TUBA1C was an independent prognostic factor for the OS of breast cancer patients. The GSEA identified that the high TUBA1C expression phenotype was differentially enriched in cell cycle, basal transcription factor, P53 signaling pathway, pathways in cancer, TOLL-like receptor signaling pathway, and NOD-like receptor signaling pathway. In summary, high messenger RNA (mRNA) expression of TUBA1C is an independent risk factor for poor prognosis of breast cancer

The metastasis patterns and their prognostic features in patients with de novo metastatic breast cancer of different ages

Abstract Purpose The prognostic outcomes of metastasis patterns in patients with de novo metastatic breast cancer (dnMBC) of different ages are unknown. Our study used a large‐scale data to investigate the metastasis patterns and prognostic features in dnMBC of different ages. Methods Total 24,698 women with dnMBC in the Surveillance, Epidemiology and End Results database (2010–2018) were divided into three groups by age. Chi‐squared test was used to compare metastasis patterns and logistic regression was performed to investigate the risk of age and specific organ metastases. Kaplan–Meier survival curves were used to compare the overall survival. Results In three groups, young group had the largest proportion of liver metastases (35.2% vs. 28.2% vs. 21.1%, p < 0.001), and elderly group had the largest proportion of lung metastases (22.6% vs. 30.0% vs. 35.0%, p < 0.001) and the lowest proportion of bone metastases (65.7% vs. 67.6% vs. 64.4%, p < 0.001). In young group, patients with liver metastases had better prognosis than patients with lung metastases (MST: 34 months vs. 29 months, p = 0.041), but in middle‐aged and elderly groups, the prognosis of lung metastases was better than that of liver metastases (MST in middle‐aged group: 24 months vs. 20 months, p = 0.002; MST in elderly group: 12 months vs. 6 months, p < 0.001). Conclusion DnMBC patients at different age have distinct metastasis patterns and prognostic features. The findings lend support to consideration of tailored management and surveillance strategies for different age patients