Background: To date, anti-angiogenic strategies in metastatic breast cancer have demonstrated benefits confined to modest improvements in progression-free survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab, an anti-VEGF receptor 2 antibody, is a human IgG1 antibody that specifically binds VEGF receptor 2 and blocks ligand stimulated activation. Early phase studies suggested anticancer effects in several solid tumors, and a phase III study demonstrated survival improvements in gastric cancer. The ROSE trial was designed to evaluate ramucirumab in the setting of HER2 negative, unresectable locally recurrent or metastatic breast cancer.

Methods: In this placebo-controlled randomized multinational phase III trial, patients with HER2 negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomized 1:2 to receive docetaxel 75 mg/m2 + placebo IV every three weeks, or to the same chemotherapy + ramucirumab 10 mg/kg IV every three weeks. Treatment was continued with each agent until investigator determined progressive disease using RECIST criteria, or until unacceptable toxicity. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographical region. An independent data monitoring committee oversaw the trial conduct, the efficacy database resides with TRIO, and this analysis was conducted by the TRIO statistical team in collaboration with Eli Lilly and Co. The primary endpoint was investigator-assessed PFS. The sample size was calculated to provide for this event-driven final PFS analysis and interim OS analysis, and a final OS analysis (to be conducted when at least 792 OS events are observed). ROSE also includes evaluation of potential predictive biomarkers.

Results: Between Aug 2008 and Dec 2011, 1144 patients were randomized. At data cut-off (March 31, 2013), median follow-up was 16.2 months. Safety, final PFS and interim OS results will be presented. Anticipated data availability is early November 2013.

Aggregated Patient Characteristics

Age (years)   24 - 82 
Prior Taxane Therapy (%) No 74 
  (%) Yes 26 
Visceral Metastasis (%) No 29 
    Yes 71 
Hormonal Receptor (%) Negative/Unknown 24 
    Positive 76 
Geographic Region (%) Americas 24 
    Asia/Middle East/Africa 12 
    Europe/Australia/New Zealand 64 
Age (years)   24 - 82 
Prior Taxane Therapy (%) No 74 
  (%) Yes 26 
Visceral Metastasis (%) No 29 
    Yes 71 
Hormonal Receptor (%) Negative/Unknown 24 
    Positive 76 
Geographic Region (%) Americas 24 
    Asia/Middle East/Africa 12 
    Europe/Australia/New Zealand 64 

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S5-04.