Ramucirumab plus docetaxel may improve progression-free survival (PFS) compared with chemotherapy alone among patients with platinum-refractory advanced urothelial carcinoma, according to a study published in The Lancet.1
A phase 2 study previously demonstrated that ramucirumab, an IgG1 monoclonal antibody that inhibits VEGFR-2, significantly improved median PFS with docetaxel compared with docetaxel alone.
For the phase 3 RANGE trial (ClinicalTrials.gov Identifier: NCT02426125), researchers randomly enrolled 530 patients with advanced or metastatic urothelial carcinoma who had progressed after 14 months or less after receiving platinum-based chemotherapy to receive ramucirumab plus docetaxel or placebo plus docetaxel. Tumor response was assessed every 6 weeks for 1 year then every 12 weeks.
Median PFS was 4.07 months (95% CI, 2.96-4.47) among patients receiving ramucirumab plus docetaxel compared with 2.76 months (95% CI, 2.60-2.96) among patients receiving placebo plus docetaxel (hazard ratio [HR], 0.757; 95% CI, 0.607-0.943; P = .0118).
Patients in the ramucirumab arm had an objective response rate of 24.5% (95% CI, 18.8-30.3) vs 14.0% (95% CI, 9.4-18.6) among patients in the placebo arm.
The most frequently reported grade 1 to 2 adverse events (AE) in either treatment group were fatigue, alopecia, diarrhea, decreased appetite, and nausea. Serious treatment-related AEs occurred in 24% and 20% of patients receiving ramucirumab and placebo, respectively, and grade 3 AEs occurred at similar rates in both arms.
The authors noted that ramucirumab plus docetaxel is first regimen to demonstrate superiority in PFS over chemotherapy alone in a phase 3 study, and concluded that the data “validate inhibition of VEGFR-2 signaling as a potential new therapeutic treatment option for patients with urothelial carcinoma.”
- Petrylak DP, de Wit R, Chi KN, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Lancet. 2017 Sep 12. doi: 10.1016/S0140-6736(17)32365-6 [Epub ahead of print]