A randomized phase II study of gemcitabine (G) alone or with pazopanib (P) in refractory soft tissue sarcoma (STS).

Abstract

11515 Background: Both G and P are active single-agents in the treatment of STS. We hypothesized that the anti-VEGF-R activity of P could augment the efficacy of G and conducted this study of G+P vs G+placebo (0). Methods: In this multi-center, double-blind study, eligibility included metastatic STS with receipt of 1–3 prior systemic regimens inclusive of an anthracycline. Patients (pts) were stratified by sarcoma subtype (liposarcoma (LPS) vs. other) and study site, then randomly assigned 1:1 to receive G 1000 mg/m2 IV over 30 minutes on days 1 and 8 every 21 days plus either P 800 mg PO or matching 0 daily. The primary endpoint was progression-free survival (PFS). Results: 54 pts were accrued from 2012–2019, Accrual was halted prior to the planned N of 80 due to withdrawal of funding. There were no differences in pt characteristics between the two arms including age (median = 60), sex (M/F 52/48%), histology (LPS 30%, leiomyosarcoma 26%, UPS 15%, synovial 11%, other 17%) and number of prior systemic therapies (median = 1). With a median follow-up of 19.1 months, PFS favored G+P and was significant using the Gehan-Wilcoxon test which favorably weighs earlier events (table). The response rate was 6.9% on the G+P arm and 8.0% on the G+0 arm; response rate was 22% for LPS treated with G+P. The most common grade ≥3 AEs (G+P v G+0) were: neutropenia (41% vs 40), hypertension (17% v 4), anemia (7% v 12). One patient died of hepatic failure on the G+P arm. Conclusions: This study demonstrated improved PFS with G+P as compared with G alone. Early termination limited statistical power. G+P is active in LPS, although P regulatory labeling currently limits use for LPS. Clinical trial information: NCT01532687 . [Table: see text]