Anlotinib for metastasis soft tissue sarcoma: A randomized, double-blind, placebo-controlled and multi-centered clinical trial.

11503 Background: No standard therapy is available in China for soft tissue sarcoma (STS) patients progressed after first-line chemotherapy. Anlotinib has shown single-agent activity in a phase II study presented orally at 2016 ASCO. This study aimed at confirming anlotinib’s efficacy and safety in advanced STS patients after failure of standard chemotherapy. Methods: Patients aged 18 years and older with angiogenesis inhibitor naive, histologically proven advanced STS, intolerance or failure to anthracycline-based chemotherapy, at least one measurable lesion according to RECIST 1.1, were eligible. Those patients were randomly assigned (2:1) to receive anlotinib (12 mg per day 2 weeks on and 1 week off) or placebo. The pathologic subtypes enrolled were: synovial sarcoma (SS), alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS) and others. Different pathologic subtypes were also randomly assigned (2:1) to each arm. The primary endpoint was progression-free survival (PFS). This trial was registered with ClinicalTrials.gov, number NCT02449343. Results: 233 patients were randomly assigned to either anlotinib (n = 158) or placebo (n = 75) and included in the final analysis. The median PFS was 6.27 months (95% CI: 4.30-8.40) for anlotinib compared with 1.47 months (95% CI: 1.43-1.57) for placebo (HR=0.33, p < 0.0001); objective response rate was 10.13% versus 1.33% (p = 0.0145); disease control rate was 55.7% versus 22.67% (p < 0.0001). For SS (n = 57), the median PFS was 5.73 months versus 1.43 months (HR = 0.2, p < 0.0001). For ASPS (n = 56), the median PFS was 18.23 months versus 3 months (HR = 0.14, p < 0.0001). For LMS (n = 41), the median PFS was 5.83 months versus 1.43 months (HR = 0.19, p < 0.0001). The most common grade 3 or higher adverse events were hypertension (18.99% with anlotinib vs 0 with placebo, p = 0.00), gamma glutamyl transferase elevation (4.43% vs 1.33%, p = 0.44), triglyceride increase (4.43% vs 0, p = 0.10), low density lipoprotein elevation (3.16% vs 2.67%, p = 1.00), hyponatremia (3.16% vs 1.33%, p = 0.67) and neutrophil count reduction (3.16% vs 0, p = 0.18). Conclusions: Anlotinib is a new treatment option for patients with advanced STS after failure of standard chemotherapy. Clinical trial information: NCT02449343.