Background The ALTER0203 clinical trial showed that anlotinib, a multitargeted tyrosine kinase inhibitor, had antitumor effects on advanced soft tissue sarcoma (STS) after the failure of standard chemotherapy. We aimed to evaluate the real‐world efficacy and explore prognostic factors and treatment patterns of anlotinib in patients with advanced STS. Methods We retrospectively analyzed the data of patients with unresectable locally advanced or metastatic STS who received at least one dose of anlotinib from June 2018 to March 2021. The survival data were analyzed using the Kaplan–Meier method and compared using the log‐rank test. The Cox proportional hazards model was performed for multivariate analysis. Results A total of 209 patients were included. The median age was 48 (range 11–85) years. The median follow‐up, progression‐free survival, and overall survival were 18.7 months, 6.1 months [95% confidence interval (CI): 4.9–7.2], and 16.4 months (95% CI: 13.6–19.1), respectively. The objective response rate was 13.4%. Nutritional status, Eastern Cooperative Oncology Group (ECOG) performance status, and anlotinib treatment patterns (combination therapy or switch maintenance therapy vs. monotherapy) were significantly associated with progression‐free survival. Besides, pathological grade, nutritional status, ECOG performance status, and anlotinib treatment patterns were predictive of overall survival. Due to anlotinib‐related toxicity, 31 (14.8%) patients, and 25 (12.0%) patients experienced dose reduction and treatment discontinuation, respectively. Conclusion These findings confirmed the efficacy of anlotinib in patients with advanced STS in a real‐world setting. The patterns of anlotinib treatment deserve further exploration.

Background: Melanoma is the most lethal skin malignant tumor with a short survival once stepping into the metastatic status and poses a therapeutic challenge. Apatinib (a tyrosine kinase inhibitor) is a promising antiangiogenic agent for the treatment of metastatic melanoma. However, antiangiogenic monotherapy is prone to acquired drug resistance and has a limited therapeutic effect. The persistence dependence of glycolytic metabolism in antiangiogenic therapy-resistant cells provides evidence that glycolysis inhibitors may enhance the effect of antiangiogenic therapy. So, this study aimed to investigate whether WZB117 (a specific GLUT1 inhibitor) could enhance the anti-tumor effect of apatinib against melanoma and its potential mechanisms. Methods:We investigated the anti-tumor effects of apatinib alone or in combination with WZB117 on human melanoma cell lines (A375 and SK-MEL-28). The MTT assay determined cell viability and the half-maximal inhibitory concentration (IC50). Multiple drug effect/combination indexes (CI) analysis was conducted to assess interactions between apatinib and WZB117. Signal transducer and activator of transcription 3 (STAT3) pathway measured by western blotting and immunofluorescence staining. RNA expression analyses were performed using the reverse transcriptionquantitative PCR method.Results: Apatinib and WZB117 showed dose and time-dependent growth inhibitory effects in both melanoma cells. The IC50 of apatinib at 48 h in A375 and SK-MEL-28 cells was 62.58 and 59.61 μM, respectively, while the IC50 of WZB117 was 116.85 and 113.91 μM, respectively. The CI values of the two drugs were 0.538 and 0.544, respectively, indicating a synergistic effect of apatinib combined with WZB117. We also found that glucose consumption and lactate production were suppressed by apatinib plus WZB117 in a dosedependent manner, paralleled by reducing glycolytic enzyme pyruvate kinase M2 (PKM2). The potential mechanism of the combination was to suppress the phosphorylation of STAT3. Knockdown of STAT3 by siRNA inhibited the expression of PKM2, while the activation of STAT3 by IL-6 increased the expression of PKM2. The effects of IL-6 were attenuated by apatinib combined with WZB117 treatment.