The combination of ramucirumab and docetaxel prolonged progression-free survival (PFS) over chemotherapy alone in patients with platinum-refractory advanced urothelial carcinoma, according to late-breaking results of a phase III trial (abstract LBA 4_PR). This is the first time that a regimen was shown to improve outcomes over chemotherapy in this setting.
“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,” said Daniel P. Petrylak, MD, of Yale University School of Medicine in New Haven, Connecticut.
Checkpoint inhibitors have been found to be effective in approximately 25% of patients, but few options have existed for those who do not respond. A phase II study of the VEGFR-2 antibody ramucirumab found a near-doubling of PFS compared with docetaxel alone.
Petrylak presented results of the phase III RANGE trial at the European Society for Medical Oncology (ESMO) 2017 Congress, held September 8–11 in Madrid. It included 530 patients with advanced or metastatic urothelial carcinoma, all of whom had progressed on first-line platinum-based chemotherapy within the previous 14 months. Patients were randomized to either ramucirumab plus docetaxel (263 patients) or to placebo plus docetaxel (267 patients).
The median PFS with ramucirumab was 4.07 months, compared with 2.76 months without it, for a hazard ratio (HR) of 0.757 (95% CI, 0.607–0.943; P = .0118). A blinded central analysis showed consistent PFS results, with an HR of 0.672 (95% CI, 0.536–0.842; P = .0005).
The objective response rate in a 437-patient intention-to-treat population was 24.5% with ramucirumab and 14.0% in the chemotherapy plus placebo arm. The overall survival data are immature at this point.
Toxicity was similar between the groups, with similar rates of grade 3 or higher adverse events and no unexpected toxicities. Neutropenia was the most common grade 3 or higher adverse event in either arm, at 15% in the ramucirumab arm and 14% in the chemotherapy plus placebo arm. Global quality-of-life scores showed no differences between the groups.
“This is the first trial to show a PFS benefit compared to chemotherapy alone in patients with platinum-refractory urothelial cancer,” said Richard Cathomas, MD, of Kantonsspital Graubünden in Chur, Switzerland, who commented on the study. “However, the magnitude of benefit was 1.3 months and, while statistically significant, it raises the question of whether it is clinically relevant.”
He said that it will be important to see if the PFS benefit eventually translates into an overall survival benefit. “We have seen from other trials combining chemotherapy with angiogenesis inhibitors in different cancers that such a small PFS benefit often does not translate into overall survival,” he said.