Abstract
BACKGROUND: Angiosarcomas are rare tumors of vascular or lymphatic origin with clinically heterogeneous presentation and behavior, predominantly originating in the skin of the head and neck and the breast area. Given their location and/or rapid progression, surgical resection is frequently not feasible, even in those with localized diseases. Conventional cytotoxic chemotherapy has proven largely ineffective against angiosarcoma. In this prospective, phase II study, we evaluated the efficacy and toxicity of paclitaxel plus avelumab as first-line therapy for unresectable angiosarcoma. PATIENTS AND METHODS: This study included patients with unresectable locally advanced or metastatic angiosarcomas, who did not receive systemic treatment. Paclitaxel (80 mg/m(2)) was intravenously infused on days 1, 8, and 15 of every 28-days cycle; avelumab (10 mg/kg) was intravenously infused every 2 weeks. Treatment continued until disease progression, unacceptable toxicity, death, or withdrawal of consent, whichever occurred first. The primary endpoint was the objective response rate (ORR); secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety profiles. RESULTS: The final analysis included 32 patients (21 male and 11 female). The median age was 63.5 years (range 27-82 years). The ORR was 50.0% (n = 16), including one complete response. Median OS and PFS were 14.5 [95% confidence interval (CI) 9.4-24.6 months] and 6.0 (95% CI 5.4-9.5 months), respectively. Among patients who received at least one treatment dose (n = 33), adverse events (AEs) of any grade were reported in 90.9% (n = 30), and severe AEs in 12.1% (n = 4), including one death. The most common hematologic and non-hematologic AEs were neutropenia (n = 13, 39.4%) and pain (n = 12, 36.4%). Immune-related pneumonitis was reported in two patients. CONCLUSION: Avelumab plus weekly paclitaxel demonstrated preliminary evidence of efficacy and tolerability in inoperable angiosarcoma. Given the rarity of angiosarcoma, further multicenter, collaborative, and translational studies are warranted.