PURPOSE: To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients with castration-resistant prostate cancer (CRPC). EXPERIMENTAL DESIGN: This double-blinded phase II study randomized (1:1:1) patients with progressive, taxane-refractory CRPC to receive MP (12 mg/m(2) i.v. day 1, 5 mg twice a day orally days 1-21, respectively) plus 15 mg/kg rilotumumab, 7.5 mg/kg rilotumumab, or placebo (i.v. day 1) every 3 weeks. The primary endpoint was overall survival (OS). RESULTS:One hundred and forty-four patients were randomized. Median OS was 12.2 versus 11.1 months [HR, 1.10; 80% confidence interval (CI), 0.82-1.48] in the combined rilotumumab versus control arms. Median progression-free survival was 3.0 versus 2.9 months (HR, 1.02; 80% CI, 0.79-1.31). Treatment appeared well tolerated with peripheral edema (24% vs. 8%) being more common with rilotumumab. A trend toward unfavorable OS was observed in patients with high tumor MET expression regardless of treatment. Soluble MET levels increased in all treatment arms. Total HGF levels increased in the rilotumumab arms. Rilotumumab showed linear pharmacokinetics when co-administered with MP. CONCLUSIONS:Rilotumumab plus MP had manageable toxicities and showed no efficacy improvements in this estimation study. High tumor MET expression may identify patients with CRPC with poorer prognosis.
RCT Entities:
PURPOSE: To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients with castration-resistant prostate cancer (CRPC). EXPERIMENTAL DESIGN: This double-blinded phase II study randomized (1:1:1) patients with progressive, taxane-refractory CRPC to receive MP (12 mg/m(2) i.v. day 1, 5 mg twice a day orally days 1-21, respectively) plus 15 mg/kg rilotumumab, 7.5 mg/kg rilotumumab, or placebo (i.v. day 1) every 3 weeks. The primary endpoint was overall survival (OS). RESULTS: One hundred and forty-four patients were randomized. Median OS was 12.2 versus 11.1 months [HR, 1.10; 80% confidence interval (CI), 0.82-1.48] in the combined rilotumumab versus control arms. Median progression-free survival was 3.0 versus 2.9 months (HR, 1.02; 80% CI, 0.79-1.31). Treatment appeared well tolerated with peripheral edema (24% vs. 8%) being more common with rilotumumab. A trend toward unfavorable OS was observed in patients with high tumor MET expression regardless of treatment. Soluble MET levels increased in all treatment arms. Total HGF levels increased in the rilotumumab arms. Rilotumumab showed linear pharmacokinetics when co-administered with MP. CONCLUSIONS:Rilotumumab plus MP had manageable toxicities and showed no efficacy improvements in this estimation study. High tumor MET expression may identify patients with CRPC with poorer prognosis.
Authors: Andreas Varkaris; Paul G Corn; Nila U Parikh; Eleni Efstathiou; Jian H Song; Yu-Chen Lee; Ana Aparicio; Anh G Hoang; Sanchaika Gaur; Lynnelle Thorpe; Sankar N Maity; Menashe Bar Eli; Bogdan A Czerniak; Yiping Shao; Mian Alauddin; Sue-Hwa Lin; Christopher J Logothetis; Gary E Gallick Journal: Clin Cancer Res Date: 2015-08-13 Impact factor: 12.531
Authors: Ahmad A Tarhini; Imran Rafique; Theofanis Floros; Phu Tran; William E Gooding; Liza C Villaruz; Timothy F Burns; David M Friedland; Daniel P Petro; Mariya Farooqui; Jose Gomez-Garcia; Autumn Gaither-Davis; Sanja Dacic; Athanassios Argiris; Mark A Socinski; Laura P Stabile; Jill M Siegfried Journal: Cancer Date: 2017-05-04 Impact factor: 6.860