First-line Anlotinib plus Anthracyclines and Ifosfamide Followed by Anlotinib Maintenance in Advanced Soft-Tissue Sarcoma: A Phase II Single-Arm Trial

Abstract Purpose: This study evaluated the efficacy and safety of first-line anlotinib combined with anthracyclines and ifosfamide, followed by anlotinib maintenance therapy, in patients with advanced soft-tissue sarcoma. Patients and Methods: Patients received four to six cycles of combination therapy administered every 21 days, comprising anlotinib (12 mg orally daily on days 1–14), anthracyclines (epirubicin 40 mg/m2 daily on days 1–2 or liposomal doxorubicin 30 mg/m2 on day 1), and ifosfamide (2 g/m2 daily on days 1–3). Following induction therapy, patients without disease progression continued anlotinib maintenance until progression, unacceptable toxicity, or death. The primary endpoint was the objective response rate. Secondary endpoints included the disease control rate, progression-free survival, overall survival, and adverse events (AE). The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100054711). Results: A total of 52 patients were enrolled. The objective response rate was 30.8% [95% confidence interval (CI), 18.7%–45.1%], and the disease control rate was 82.7% (95% CI, 69.7%–91.8%). With a median follow-up of 29.9 months (95% CI, 24.6–32.3), the median progression-free survival was 6.2 months (95% CI, 2.6–11.2). The median overall survival was not reached (95% CI, 14.4–not estimable). Treatment-related AE of any grade occurred in all patients. The most frequently reported AE included nausea (100%), fatigue (86.5%), and hypoalbuminemia (44.2%). The most common grade 3 to 4 AE included anemia (23.1%), leukopenia (17.3%), and thrombocytopenia (9.6%). No treatment-related deaths occurred. Conclusions: First-line anlotinib combined with anthracyclines and ifosfamide, followed by anlotinib maintenance, demonstrated encouraging efficacy with acceptable toxicities in patients with advanced soft-tissue sarcoma, warranting further investigation in randomized controlled trials.