Utidelone in patients with advanced soft tissue sarcoma refractory to anthracycline and antiangiogenic therapy (UTISARC): a single-arm phase II study

BACKGROUND: Treatment options remain limited for patients with advanced or metastatic soft tissue sarcoma after failure of both anthracycline-based chemotherapy and antiangiogenic therapy. Utidelone, an epothilone analog, has demonstrated antitumor activity across a broad spectrum of preclinical models and clinical trials. This single-arm, phase II trial was designed to assess the efficacy and safety of utidelone in a heavily pretreated population. METHODS: This study enrolled patients aged 18 years or older with locally advanced or metastatic soft tissue sarcoma who had previously been treated with anthracycline-based chemotherapy and antiangiogenic tyrosine kinase inhibitors. Participants received utidelone via a 90-minute intravenous infusion at a dose of 30 mg/m² on days 1-5 of each 21-day treatment cycle, continuing until disease progression or the occurrence of unacceptable toxicity. The primary endpoint was median progression-free survival. The secondary endpoints included the objective response rate, overall survival and safety. RESULTS: Between August 2022 and March 2025, a total of 27 patients were included in the study. The median age was 55 years (range, 30-68). There were 15 patients with leiomyosarcoma, 3 with dedifferentiated liposarcoma, 3 with epithelioid sarcoma, 2 with angiosarcoma, and 4 with other types of sarcoma. The median number of prior systemic therapy regimens was 2 (range, 1-4). The median treatment exposure was 5 cycles (range, 1-10). Two patients achieved a partial response, resulting in an objective response rate of 7%. The median progression-free survival was 4.6 months (95% confidence interval, 3.6-5.6). Overall survival data were immature, with only 9 death events (33%) observed. The estimated 12-month overall survival rate was 80%. Most adverse events were grade 1 or 2 in severity. The most frequently observed grade ≥ 3 adverse event was peripheral neuropathy (11%). CONCLUSIONS: In this exploratory trial, utidelone demonstrated preliminary antitumor activity and a manageable safety profile in patients with refractory soft tissue sarcoma. Further exploration of novel combination therapies involving utidelone is warranted to enhance its clinical utility. TRIAL REGISTRATION: ChiCTR2200062161, registered on July 26, 2022.