Evaluation Of Thyroid-Stimulating Hormone-Increased, Hypertriglyceridemia And Proteinuria As Markers Of Anlotinib Efficacy In Advanced Soft Tissue Sarcoma.

e23548 Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. The most common adverse events with anlotinib were hypertension (62.66%), thyroid stimulating hormone (TSH) increased (56.33%), hypertriglyceridemia (50%), hand-foot syndrome (48.10%) and proteinuria (36.08%) similar to other vascular endothelial growth factor receptor pathway-targeted therapies. We had evaluated the anlotinib-induced hand-foot syndrome and hypertension with clinical outcome in aSTS patients previously. Here we investigated thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria on clinical outcome in aSTS patients treated with anlotinib. Methods: We conducted a review of patients enrolled in ALTER0203. Median PFS was analyzed in patients with thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria vs patients with no thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria. All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. During the study, TSH increased was observed in 89 patients (56.33%). Hypertriglyceridemia was observed in 79 patients (50%). Proteinuria was observed in 57 patients (36.08%). Median PFS was longer in patients with TSH increased vs patients with no TSH increased (8.40 vs 4.23 months, p = 0.015). Patients with any grade TSH increased while on anlotinib had an adjusted hazard ratio for progression of 0.64 compared to those without TSH increased. Also, median PFS was longer in patients with hypertriglyceridemia and proteinuria vs patients with no hypertriglyceridemia and proteinuria (8.43 vs 4.13 months, p = 0.002; 8.40 vs 4.37, P = 0.048). Patients with any grade hypertriglyceridemia and proteinuria while on anlotinib had an adjusted hazard ratio for progression of 0.59 and 0.75 compared to those without hypertriglyceridemia and proteinuria respectively. Conclusions: In this retrospective analyses, TSH increased, hypertriglyceridemia and proteinuria can serve as biomarkers in aSTS patients treated with anlotinib. Clinical trial information: NCT02449343 .