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.

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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.”

Reference

  1. 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]