A phase II study of epirubicin combined with anlotinib followed by anlotinib in the first-line treatment of advanced unresectablesoft tissue sarcoma.

e23536 Background: Anlotinib, a multi-target TKI,showed well efficiency and tolerance for the treatment of recurrent or metastatic soft tissue sarcoma (STS). Moreover, the synergistic activity of anlotinib plus epirubicin on the sarcoma PDX modelwas confirmed in our previous preclinical study. This phase II clinical study was designed to assess the efficacy and safety of epirubicin combined with anlotinib followed by anlotinib in the first-line treatment of advanced unresectable STS. Methods: This study is an open-label, prospective, single-arm phase II clinical study. Patients (pts) with locally advanced or metastatic soft tissue sarcomas confirmed by histopathology and not suitable for surgery were recruited, and treated with 6 cycles of anlotinib and epirubicin (epirubicin 90mg/m2 CIV for 48 hours on day 1 and anlotinib 12 mg QD on day1-14, 21 days per cycle), followed by anlotinib alone unless the pts experienced progression or intolerance. Tumor imaging evaluations and echocardiography were performed every 2 cycles during combined therapy, and were performed every 3 cycles during the sequential anlotinib treatment. The primary end point was the progression-free rate at 12 weeks (PFR12w) and 6 months (PFR6m), secondary endpoints included ORR, PFS, safety, DCR and OS. Results: 33 eligible pts were enrolled from June 2019 to August 2020, and 3 pts dropped out without completing one cycle of treatment. Of 30efficacy-evaluable pts,10 were man, median age was 48 (range 18-74). The main subtypes included 10 leiomyosarcoma, 8 fibrosarcoma, 5 dedifferentiated liposarcoma, 4 synovial sarcoma, 2 undifferentiated pleomorphic sarcoma, and 1 epithelioid sarcoma. The average number of combined treatment cycle is 4.7 (range 2-6), 13 pts had entered into anlotinib maintenance treatment. The PFR12w, PFR6m, ORR, DCR were 70%,53.8%, 13.3%, and 80%,respectively. Median PFS was 11.5 months (95%CI: 5.0-NA), median OS has not been reached. As cut-off on Jan 20th 2020, 6 pts are still in treatment. The other pts discontinued trial due to disease progression (16/24), adverse events (AEs) (3/24), changes in treatment strategy because of tumor shrinkage (3/24), cytoreductive surgery (1/24), and opt-out (1/24). The main AEs were grade III-IV neutropenia (8/30, 26.7%), and 7 of them were febrile neutropenia (7/30, 23.3%). Until now, no cardiac-related AEswere observed. Conclusions: Advanced unresectable STS pts could benefit from epirubicin combined with anlotinib followed by anlotinibtreatment in first line. And it is generally well tolerated especially with no short-term cardiac toxicity. Clinical trial information: ChiCTR1900024928.