Related Experiment Video
Updated: May 17, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Targeted MET inhibition in castration-resistant prostate cancer: a randomized phase II study and biomarker analysis
Charles J Ryan1, Mark Rosenthal, Siobhan Ng
1University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, USA. ryanc@medicine.ucsf.edu
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.
Insights
Rilotumumab combined with chemotherapy did not improve survival for castration-resistant prostate cancer (CRPC) patients. High tumor MET expression may indicate a poorer prognosis in CRPC.
Area of Science:
- Oncology
- Medical Research
Background:
- Castration-resistant prostate cancer (CRPC) remains a significant clinical challenge.
- Hepatocyte growth factor (HGF)/scatter factor signaling, mediated by the MET receptor tyrosine kinase, is implicated in cancer progression.
Purpose of the Study:
- To assess the efficacy, safety, and pharmacokinetic profile of rilotumumab, a monoclonal antibody targeting HGF, when administered with mitoxantrone and prednisone (MP) in CRPC patients.
- To explore potential biomarkers, including MET expression, associated with treatment response.
Main Methods:
- A double-blinded, randomized phase II clinical trial.
- Patients with progressive, taxane-refractory CRPC received MP plus either 15 mg/kg rilotumumab, 7.5 mg/kg rilotumumab, or placebo every 3 weeks.
- Overall survival (OS) was the primary endpoint.
Main Results:
- No significant improvement in median overall survival (12.2 vs. 11.1 months) or progression-free survival was observed in the rilotumumab arms compared to placebo.
- Peripheral edema was a more frequent adverse event in patients receiving rilotumumab.
- A trend towards worse OS was noted in patients with high tumor MET expression, irrespective of treatment arm.
- Pharmacokinetic analysis indicated linear rilotumumab pharmacokinetics when co-administered with MP.
Conclusions:
- Rilotumumab in combination with MP demonstrated manageable toxicity but did not enhance efficacy in this CRPC study.
- Elevated tumor MET expression may serve as a prognostic indicator for poorer outcomes in CRPC patients.
