Pazopanib for Metastatic Soft Tissue Sarcoma (Sts) with or Without Denosumab

Abstract

ABSTRACT Aim: Soft tissue sarcoma (STS) is such a rare neoplasm that we organized Cure-Sarcoma Therapuetic Consortium, including pahologists, gastroenerologists, surgeons and medical oncologists in Japan. We conducted a retrospective analysis on pazopanib for metastatic STS in order to examine the relationships of PFS with or without denosumab, also from the viewpoint of the first-line setting of pazopanib for metastatic diseases. Methods: In this study, the patients with metastatic STS treated with pazopanib from November 2012 till March 2014, conseutively, were retrospectively analyzed. Among the first four months, the starting dose of pazopanib was fixed at 800mg, but later it was changed to 400mg because of severe adverse events. Results: Forty six patients (23 leiomyosarcomas, 5 liposarcomas, 18 other subtypes) were identified. Median age was 56 years old (range 17-81), 38 females and 8 males, ECOG PS was 0/1 of 39 patients and 2/3 of 7 patients, 25 patients were in the first-line setting and 21 patients were in the second or later-line settings and 17 patients with multiple bone metastases were all treated with both pazopanib and denosumab. All the patients were evaluable by RECIST 1.1, and 24 patients were evalated as PR/SD but on the other hand, 22 patients showed PD/NE. After a median observation period of 27 weeks (range 6-69), OS was not reached yet (95% CI: 30.7-) and median PFS was 9.7 weeks (95%CI: 8.4-12.0). From the view point of PFS with response, PFS in PR and that in SD was similar. PFS showed no differences between 800mg vs 400mg (p=0.3449), leiomyosarcoma vs liposarcoma vs other subtypes (p=0.6296), and PS 0/1 vs 2/3 (p=0.7847). But PFS in PR/SD was longer (23.6 weeks) than that in SD/NE (6.1 weeks, p=0.0001). Finally, PFS with denosumab was not inferior to that without denosumab (p=0.25). Conclusions: Pazopanib including first-line setting for metastatic STS is effective and it is comparable with EORTC trials. The combination chemotherapy of pazopanib with denosumab is promising and further investigations are warranted. Disclosure: All authors have declared no conflicts of interest.