Ramucirumab/Docetaxel Improved Progression-Free Survival in Advanced Urothelial Carcinoma

A significant progression-free survival and overall response rate improvement was seen in patients with advanced urothelial carcinoma treated with the combination of the VEGFR-2 antagonist ramucirumab (Cyramza) plus docetaxel, according to interim results from an open-label, phase II study presented at the 2015 Genitourinary Cancers Symposium (abstract 295).

“Ramucirumab combined with docetaxel conferred a statistically significant progression-free survival improvement of greater than 11.5 weeks at the median, reducing the risk of disease progression by 61%,” said Daniel P. Petrylak, MD, of Yale University Medical Center.

Current standard of care for patients with metastatic bladder cancer is a cisplatin/gemcitabine or MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) regimen, with docetaxel used as a palliative care option. Those patients with metastatic disease who progress after first-line treatment has fewer treatment options, Petrylak explained.

Previous clinical trials have shown that ramucirumab improved overall survival alone or in combination in patients with gastric cancer, colorectal cancer, and lung cancer.  

This study enrolled patients with metastatic transitional cell carcinoma who had relapsed within 1 year from a platinum-based regimen. Patients were randomly assigned to intravenous docetaxel 75 mg/m² with intravenous ramucirumab 10 mg/kg (n=46), docetaxel alone (n=44), or docetaxel plus the VEGFR-1 antagonist icrucumab 12 mg/kg (n=49). The primary endpoint of the analysis was progression-free survival.

Results showed that patients assigned to combination treatment with docetaxel/ramucirumab had a reduced risk for disease progression (hazard ratio [HR] = 0.388). The median progression-free survival in patient's assigned docetaxel/ramucirumab was 22.0 weeks vs 10.4 weeks for docetaxel alone, and 7.0 weeks for icrucumab/docetaxel. A subgroup analysis showed that treatment with ramucirumab/docetaxel was favored regardless of age, sex, ECOG performance status, prior anti-angiogenic therapy, visceral metastases, liver metastases, or type of prior platinum-based therapy.  

 “Overall survival data is not mature at this point, but at this point the overall survival for docetaxel is 33.4 weeks, the ram/docetaxel arm is 48.9 weeks and the ICR/docetaxel arm 27.7 weeks,” Petrylak said. “This is nonsignificant, but, again, it is not yet mature.”

Patients assigned ramucirumab had an overall response rate of 20% compared with 5% for patients given docetaxel alone (P = .05) and 10% in the icrucumab/docetaxel arm. 

There was a difference of 5% or greater in the following adverse events for patients assigned ramucirumab compared with docetaxel: fatigue (33% vs 11%), febrile neutropenia (20% vs 11%), diarrhea (7% vs 2%), stomatitis (7% vs 0%), and thrombocytopenia (7% vs 0%).

“These results support the initiation of the RANGE trial, which is a randomized registration phase III trial comparing docetaxel combined with placebo to docetaxel combined with ramucirumab at the same dose and schedule used in our trial,” Petrylak said.