Phase II trial of gemcitabine and docetaxel with bevacizumab in soft tissue sarcoma

Gemcitabine (g) and docetaxel (d) are commonly used to treat recurrent/metastatic soft tissue sarcoma. this study tested the hypothesis that outcomes would be improved by addition of bevacizumab (b). the initial design was randomized double-blind trial of g + d + b versus g + d + placebo. due to slow accrual this was modified to single-arm open-label g + d + b. eligible patients had diagnosis of leiomyosarcoma,pleomorphic undifferentiated sarcoma,pleomorphic liposarcoma,or angiosarcoma. treatment was b 15 mg/kg on d1,g 900 mg/m2 on d1 and d8,and d 75 mg/m2 on d8,q21d. primary endpoint was progression-free survival (pfs) at 6 months and would be met if ≥17 patients were progression-free at 6 m. secondary endpoints are response rate,pfs at 3 m,overall survival,and toxicity. of 44 patients enrolled,35 were treated with gdb and evaluable for safety and efficacy. median age was 55,50% male,most ecog 0. toxicity is mostly myelosuppression with one deep vein thrombosis and one small bowel perforation possibly related to b. there were 17 partial responses (49%) by recist 1.1. among 35 patients,the number who remained on study and progression-free was 24 at 3 m and 15 at 6 m. 9 withdrew prior to 6 m for reasons other than toxicity or progression. pfs at 6 m was 65% (95% ci: 51-85%). the primary endpoint of 6 m pfs was not met due to censoring of patients who withdrew. however pfs at 3 m (76%) was promising and response rate was higher than expected from g + d. © 2015 mark a. dickson et al.