Isabelle L. Ray-Coquard, Philippe A. Cassier, and Jean-Yves Blay, Centre Léon Bérard and Claude Bernard University, Lyon; Julien Domont, Olivier Mir, and Axel Le Cesne, Gustave Roussy, Villejuif; Emmanuelle Tresch-Bruneel and Stéphanie Clisant, Centre Oscar Lambret; Nicolas Penel, Centre Oscar Lambret and Lille-Nord-de-France Medical School, Lille; Emmanuelle Bompas, Centre René Gauducheau, Nantes; Sophie Piperno-Neumann, Institut Curie, Paris; Antoine Italiano, Institut Bergonié, Bordeaux; Christine Chevreau, Institut Claudius Regaud, Toulouse; Didier Cupissol, Institut de Cancérologie de Montpellier, Val d'Aurelle, Montpellier; François Bertucci, Institut Paoli Calmette, Marseille; Jacques-Olivier Bay, Centre Jean Perrin, Clermont-Ferrand; Olivier Collard, Institut de Cancérologie de la Loire Lucien Neuwirth, Saint Priest en Jarez; Esma Saada-Bouzid, Centre Antoine Lacassagne, Nice; Nicolas Isambert, Centre Georges-François Leclerc, Dijon; and Corinne Delcambre, Centre François Baclesse, Caen, France.
J Clin Oncol. 2015 Sep 1;33(25):2797-802. doi: 10.1200/JCO.2015.60.8505. Epub 2015 Jul 27.
The aim of this randomized, phase II trial was to explore the activity and safety of adding bevacizumab to paclitaxel once per week in treatment of angiosarcomas (AS).
Patients were treated with paclitaxel alone (90 mg/m(2) per week for six cycles of 28 days each; arm A) or with paclitaxel combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the combination treatment arm, bevacizumab was administered after the six cycles of chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until intolerance or progression occurred. Stratification factors were superficial versus visceral AS and de novo versus radiation-induced AS. The primary end point was the 6-month progression-free survival (PFS) rate, which was based on RECIST, version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b = 20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS rate at 6 months defining promising drug.
A total of 52 patients were enrolled, and 50 were randomly assigned in 14 centers. The most common primary sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24 (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and 1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months. Both treatment regimens were considered active, with 6-month PFS rates of 54% (14 of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the combination arm and included one fatal drug-related toxicity (intestinal occlusion).
The primary objective was met in both treatment arms. However, the present data do not support additional clinical investigation of combined paclitaxel/bevacizumab for the treatment of advanced AS.
本随机、二期临床试验旨在探讨每周一次给予紫杉醇联合贝伐单抗治疗血管肉瘤（AS）的疗效和安全性。
患者接受紫杉醇单药治疗（每周 90mg/m2，每 28 天为一周期，共 6 个周期；A 组）或紫杉醇联合贝伐单抗治疗（每两周 10mg/kg，B 组）。在联合治疗组中，在 6 个周期化疗后，贝伐单抗作为维持治疗（每 3 周 15mg/kg）给药，直至出现不耐受或疾病进展。分层因素为表浅性 AS 与内脏性 AS，以及新发 AS 与放射性 AS。主要终点为基于 RECIST 1.1 版的 6 个月无进展生存（PFS）率。统计假设为 P0=20%，P1=40%，α=10%，β=20%。P0 定义为 6 个月时无进展定义为药物无效，P1 定义为 6 个月时 PFS 率有希望定义为药物有效。
共纳入 52 例患者，在 14 个中心按 1:1 比例随机分组。最常见的原发部位为乳房（49%）和皮肤（12%）。内脏性 AS 17 例（34%），放射性 AS 24 例（49%）。体能状态为 0 分 24 例（49%），1 分 25 例（51%）。中位随访时间为 14.5 个月。A 组和 B 组 6 个月 PFS 率分别为 54%（14/26）和 57%（14/24），均认为治疗有效。A 组和 B 组的中位总生存时间分别为 19.5 个月和 15.9 个月。联合治疗组毒性更高，包括 1 例与药物相关的致命毒性（肠闭塞）。
两组治疗均达到了主要研究终点。然而，目前的数据不支持进一步研究紫杉醇联合贝伐单抗治疗晚期 AS。
