Pink Daniel, Andreou Dimosthenis, Bauer Sebastian, Brodowicz Thomas, Kasper Bernd, Reichardt Peter, Richter Stephan, Lindner Lars H, Szkandera Joanna, Grünwald Viktor, Kebenko Maxim, Kirchner Marietta, Hohenberger Peter
Department of Hematology, Oncology and Palliative Medicine, Helios Hospital Bad Saarow, Sarcoma Center Berlin-Brandenburg, 15526 Bad Saarow, Germany.
Department of Internal Medicine C, University Hospital Greifswald, 17475 Greifswald, Germany.
Cancers (Basel). 2021 Mar 11;13(6):1223. doi: 10.3390/cancers13061223.
We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7-15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, = 0.0247) and PFS (11.3 vs. 2.7 months, < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.
我们旨在评估紫杉醇联合帕唑帕尼治疗晚期血管肉瘤（AS）的疗效和毒性。主要终点是六个月时的无进展生存率（PFSR6）。计划入组44例患者，以检测PFSR6>55%的情况，并对前14例患者进行中期无效性分析。该研究未达到预定的中期目标，即6个月时14例患者中有6例无进展。在这一结果出现时，2014年7月至2016年4月期间已入组26例患者，超出计划12例。经过中位9.5（IQR 7.7 - 15.4）个月的随访，PFSR6为46%。2例患者完全缓解，7例患者部分缓解。与内脏型AS患者相比，浅表型AS患者的PFSR6（61%对13%，P = 0.0247）和PFS（11.3个月对2.7个月，P < 0.0001）显著更高。整个队列的中位总生存期为21.6个月。5例患者共报告了10例与药物相关的严重不良反应，包括1例致命性肝衰竭。尽管我们的研究未达到主要终点，但浅表型AS患者11.6个月的中位PFS似乎很有前景。考虑到近期的报告，未来的研究应在随机、多组的情况下评估VEGFR和免疫检查点抑制剂联合或不联合紫杉醇的安全性和疗效。
