Phase II Trial Shows Benefit of Adding Ramucirumab to Docetaxel in Previously Treated Advanced Urothelial Carcinoma
Adding the anti–vascular endothelial growth factor receptor 2 (VEGFR-2) antibody ramucirumab to docetaxel improved progression-free survival among previously treated patients with locally advanced or metastatic urothelial carcinoma, reported Petrylak et al in the Journal of Clinical Oncology. However, no benefit was seen with the addition of the anti–VEGFR-1 antibody icrucumab to docetaxel.
Study Details
In the open-label study, 140 patients with diseaes progression during or within 12 months of platinum-based therapy were randomly assigned 1:1:1 to receive intravenous (IV) docetaxel at 75 mg/m2 on day 1 (n = 45), docetaxel plus IV ramucirumab at 10 mg/kg on day 1 (n = 46), or docetaxel on day 1 plus IV icrucumab at 12 mg/kg on days 1 and 8 (n = 49) of 21-day cycles. Treatment was continued until disease progression or unacceptable toxicity.
The primary endpoint was investigator-assessed progression-free survival. Overall, 98% of patients had received no prior antiangiogenic therapy, and 71% had visceral metastases.
Progression-Free Survival
Median progression-free survival was 2.8 months (95% confidence interval [CI] = 1.9–3.6 months) in the docetaxel group, 5.4 months (95% CI = 3.1–6.9 months) in the ramucirumab/docetaxel group (stratified hazard ratio [HR] = 0.389, P = .0002, vs docetaxel), and 1.6 months (95% CI = 1.4–2.9 months) in the icrucumab/docetaxel group (HR = 0.863, P = .5053). Response rates were 9%, 24%, and 12%, respectively.
Adverse Events
The most common grade ≥ 3 adverse events were neutropenia (36% in the docetaxel group, 33% in the ramucirumab/docetaxel group, 39% in the icrucumab/docetaxel group); fatigue (13%, 30%, 20%); febrile neutropenia (13%, 17%, 6%); and anemia (7%, 13%, 14%). Adverse events led to discontinuation of any study drug in 16%, 41%, and 18% of patients, respectively.
The investigators concluded: “The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging [progression-free survival] in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.”
The study was supported by Eli Lilly.
Daniel P. Petrylak, MD, of Yale School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
