Pazopanib for soft tissue sarcoma (STS) in the first- line setting with denosumab.

10567 Background: We established the Japan Sarcoma Association and hold the Japan-United States International Workshop on the Sarcoma Research and Therapy in December 2014. Aim: We conducted a retrospective analysis on pazopanib for STS in order to examine the relationships of PFS with denosumab, also from the viewpoint of the first-line setting for metastatic diseases. Methods: In this study, the patients with metastatic STS treated with pazopanib from November 2012 till January 2015, consecutively, were retrospectively analyzed. Among first 4 months, the starting dose was fixed at 800mg, but later changed to 400mg because of severe adverse events. Results: Eighty seven patients (43 leiomyosarcomas, 8 liposarcomas, 36 other subtypes) were identified. Median age was 56 years old (range 17-84), 69 females and 18 males, 50 pts were treated in the first-line setting and 37 pts were in the second or later-line setting, and 26 pts with multiple bone metastases were all treated with denosumab. Remarkable severe toxicities (G 3/4) were observeded as pheumothorax, hyperbilirubinemia, bladder perforation and perianal abscess, but the rates were infrequent ( < 2.2%). All hypertension was manageable by anti-hypertensive medication and cardio-echogram showed no decrease of EF and it was definitly < 10%. But seum BNP increaseded in some pts. No pts showed symptomatic heart failure in the observation period (median: one year). All the pts, included till July 2014, were evaluable by RECIST 1.1, and 37 pts were evaluated as PR/SD and 31 pts showed PD/NE. Median OS reached 16.9 months (95%CI: 9.7-ND) and median PFS was 2.6 months (95%CI: 2.2-3.7). From the viewpoint of PFS with response, PFS in PR and that in SD were similar. PFS showed no differences between 800mg vs 400mg, leiomyosarcoma vs liposarcoma vs others, PS 0/1 vs 2/3 and 1st line vs later line. But PFS in PR/SD was longer (4.9 months, 95%CI: 2.8-7.1) than that in PD/NE (1.7 months, 95%CI: 1.1-2.3, p < 0.0001). PFS with denosumab was not inferior to that without denosumab. Conclusions: Pazopanib including first-line setting for metastatic STS is effective and comparable with EORTC trials. The combination chemotherapy of pazopanib with denosumab is promising and further investigations are warranted.