Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Internal Medicine, Division of Hematology/Oncology and BMT, University of Iowa, Iowa City, IA, USA.
Br J Cancer. 2021 Aug;125(4):528-533. doi: 10.1038/s41416-021-01448-0. Epub 2021 May 28.
Pazopanib is active in refractory soft-tissue sarcoma (STS) and significantly prolongs PFS. Prior studies of combinations of metronomic topotecan with pazopanib have indicated preclinical evidence of response in patients with sarcoma.
This prospective, single arm, phase II study evaluated the efficacy of the combination of pazopanib with topotecan in patients with metastatic or unresectable non-adipocytic STS. Furthermore, it incorporated exploratory arms for osteosarcoma and liposarcoma. The primary endpoint was progression-free rate at 12 weeks in the non-adipocytic STS cohort.
57.5% of patients in the non-adipocytic STS cohort were progression free at 12 weeks, which did not meet the primary endpoint of the study (66%). The exploratory osteosarcoma cohort exceeded previously established phase II trial comparator data benchmark of 12% with a PFR at 12 weeks of 69.55%. Treatment with the combination of pazopanib and topotecan was accompanied by a grade 3 or 4 toxicities in most patients.
In this prospective trial in refractory metastatic or unresectable STS and osteosarcoma, the combination of pazopanib with topotecan did not meet its primary endpoint of progression-free rate at 12 weeks. The combination of pazopanib with topotecan was associated with a high degree of toxicity.
帕唑帕尼在难治性软组织肉瘤（STS）中具有活性，可显著延长 PFS。先前关于米托蒽醌与帕唑帕尼联合治疗的研究表明，该联合治疗在肉瘤患者中有临床前反应证据。
这项前瞻性、单臂、II 期研究评估了帕唑帕尼联合拓扑替康在转移性或不可切除的非脂肪性 STS 患者中的疗效。此外，它还纳入了骨肉瘤和脂肪肉瘤的探索性队列。非脂肪性 STS 队列的主要终点是 12 周时无进展生存率。
非脂肪性 STS 队列中有 57.5%的患者在 12 周时无进展，未达到研究的主要终点（66%）。探索性骨肉瘤队列的无进展生存率（PFR）为 69.55%，超过了之前确立的 II 期试验比较数据基准的 12%。帕唑帕尼联合拓扑替康治疗的大多数患者出现 3 级或 4 级毒性。
在这项针对难治性转移性或不可切除的 STS 和骨肉瘤的前瞻性试验中，帕唑帕尼联合拓扑替康未能达到其 12 周时无进展生存率的主要终点。帕唑帕尼联合拓扑替康治疗与高毒性相关。
