Adding ramucirumab (CYRAMZA) to standard docetaxel (Taxotere) improved progression-free survival (PFS) compared with docetaxel alone in patients with advanced or metastatic urothelial cancer who have progressed on platinum-based chemotherapy.
In the international phase III RANGE trial, PFS improved by more than 1 month by adding ramucirumab, reported Daniel P. Petrylak, MD, at the European Society for Medical Oncology 2017 Congress in Madrid.
“RANGE is the first phase III trial to demonstrate a PFS advantage over chemotherapy alone in platinum-refractory advanced or metastatic urothelial carcinoma,” he said. Further, the combination of ramucirumab and docetaxel did not result in significant additive toxicity or compromise quality of life compared with placebo plus docetaxel. Therefore, the combination represents a new treatment option for this patient population, he said.
“We don’t have other therapeutic options for patients who have failed checkpoint inhibition therapy or for patients who may not be eligible for checkpoint inhibition therapy,” said Dr. Petrylak, of Yale School of Medicine and Yale Cancer Center, New Haven, CT. “Ramucirumab plus docetaxel could become a standard of care in patients with platinum-refractory advanced or metastatic urothelial cancer who have either progressed on checkpoint inhibitors or are not eligible to receive them.”
Ramucirumab is a human IgG1 monoclonal antibody VEGFR2 antagonist that was previously shown superior to docetaxel on the endpoint of disease-free survival in a phase II study in patients with platinum-refractory urothelial carcinoma.
The phase III RANGE trial built on this experience, enrolling 530 patients with locally advanced or unresectable metastatic bladder cancer that progressed within 14 months of prior chemotherapy, either a cisplatin- or carboplatin-based regimen. Seven percent of patients in the experimental arm and 10% in the docetaxel monotherapy arm received prior checkpoint inhibitor therapy. Patients were randomized 1:1 to ramucirumab, 10 mg/kg, combined with docetaxel, 75 mg/m2 intravenously, or placebo plus docetaxel. Docetaxel was limited to six cycles, with up to four additional cycles allowed after trial sponsor approval.
Some 61% enrolled had two or more adverse prognostic risk factors at baseline, said Dr. Petrylak, confirming that the study population was “a sick group of patients.”
Median follow-up in the full intent-to-treat population was 5.0 months. Investigator-assessed median PFS, the primary endpoint, was 4.07 months with the combination therapy compared with 2.76 months for patients who received docetaxel alone (HR=0.757, p=.018). By independent blinded assessment, median PFS was 4.04 months versus 2.46 months in favor of ramucirumab/docetaxel (HR=0.672, p=.0005). At 1 year, by investigator assessment, 11.9% of patients assigned to ramucirumab and docetaxel were progression free versus 4.5% of those assigned to docetaxel alone. The corresponding percentages by independent blinded assessment were 8.3% versus 5.1%, again favoring the combination. PFS outcomes were consistent across a variety of patient subgroups.