A randomized, open‐label, phase 2, multicenter trial of gemcitabine with pazopanib or gemcitabine with docetaxel in patients with advanced soft‐tissue sarcoma
Neeta Somaiah, Brian A. Van Tine, Amy E. Wahlquist, Mohammed Milhem, Elizabeth G. Hill, Elizabeth Garrett‐Mayer, Kent Armeson, Scott M. Schuetze, Christian F. Meyer, Daniel Y. Reuben, Anthony Elias, William L. Read, Sant P. Chawla, Andrew S. Kraft
Abstract
Background Therapeutic options for patients with advanced soft‐tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS. Methods The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline‐based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m 2 on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m 2 on days 1 and 8 and docetaxel at a dose of 100 mg/m 2 on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression‐free survival (PFS) and rate of grade ≥3 adverse events (AEs) for these 2 regimens based on the intent‐to‐treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events). Results A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm ( P = .3, log‐rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade ≥3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade ≥3 AEs occurring in ≥10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively). Conclusions The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS.