一项针对晚期血管肉瘤的化疗/免疫治疗II期研究：采用节拍式吉西他滨、多柔比星、多西他赛联合nivolumab（NCT04535713）——中期分析

Background: Advanced angiosarcoma is a rare and aggressive sarcoma which is most often fatal, with a median progression free survival of 4-6 months on standard therapy. Therefore, innovative treatment regimens are urgently needed. Methods: Endpoints: Primary: Progression Free Survival; Secondary: Best overall response; Overall Survival; Incidence and severity of adverse events. Eligibility: > 18 years, confirmed diagnosis of advanced angiosarcoma, acceptable hematologic and organ function. Treatment Schedule: Gemcitabine (600 mg/m2; max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Days 1 and 8, and nivolumab (240 mg) on Day 1 of a 3-week cycle. Results: Median prior regimens = 1 (range 0-9). Efficacy: 7 of 9 patients who completed at least 2 treatment cycles and follow-up imaging (modified ITT population) were evaluated for: Median PFS: 9.4 months (95% CI: 8.224 to 9.441; 7 events, 0 censored); Best response: Confirmed 1 CR, 3 PR, 3 SD; ORR = 57%; DCR = 100%. Nine patients who received at least one dose of each chemotherapy agent (ITT population) were evaluated for: Median OS: 28.4 months (95% CI: 0.724 to 31.217; 5 events, 4 censored). Safety: 8 of 9 (89%) patients experienced a ≥ Grade 3 TRAE: leukopenia (n=6), thrombocytopenia (n=4), neutropenia (n=5), anemia (n=2), lymphopenia (n=2), fatigue (n=1), dec. LVEF (n=1), periorbital edema (n=1), limb edema (n=1) and worsening hypothyroidism (n=1). There were no Grade 5 nor unexpected adverse events. Conclusion: This metronomic chemo/immunotherapy regimen may be a synergistic and effective therapy for advanced angiosarcoma with manageable toxicity.