Ramucirumab plus docetaxel prolongs PFS in advanced urothelial cancers
medwireNews: Adding ramucirumab to docetaxel significantly improves progression-free survival (PFS) in patients with advanced or metastatic urothelial cancer who have progressed on platinum-based chemotherapy, show results from the phase III RANGE trial.
“Ramucirumab reduced the risk of disease progression by 24% and this was consistent across patient subgroups,” lead author Daniel Petrylak, from Yale School of Medicine in New Haven, Connecticut, USA, said in a press statement at the ESMO 2017 Congress in Madrid, Spain.
In addition, “[t]he objective response rate nearly doubled with ramucirumab and there were no significant differences in toxicities between treatments,” he noted.
Petrylak therefore suggested: “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.”
We found a 25% reduction in the hazard ratio for progression-free survival in favor of the combination therapy arm and also a doubling of the objective response rate in favor of ramucirumab and docetaxel.
Petrylak and team randomly assigned 530 patients with advanced or metastatic urothelial cancer who had progressed on first line platinum-based chemotherapy within the previous 14 months to receive ramucirumab 10 mg/kg plus docetaxel 75 mg/m2 on day 1 of a 21-day cycle (n=263) or to receive placebo plus docetaxel (n=267).
Median PFS was significantly longer in the ramucirumab plus docetaxel group than in the placebo plus docetaxel group, at 4.07 versus 2.76 months, giving a significant hazard ratio of 0.76.
At 6 and 12 months, 28.5% and 11.9% of patients in the ramucirumab plus docetaxel arm were free from disease progression, respectively, compared with 18.9% and 4.5% of those in the placebo plus docetaxel group.
Similar results were observed in a prespecified independent blinded assessment of disease progression, with a slight reduction in the hazard ratio to 0.67.
And the PFS benefits with ramucirumab plus docetaxel were consistent across most subgroups of patients.
The objective response rate was also higher with ramucirumab plus docetaxel than with placebo plus docetaxel, at 24.5% versus 14.0%, but overall survival data has not yet reached maturity.
Petrylak et al found that rates of adverse events of grade 3 or above were similar between the groups, with the exception of anemia, which was lower with ramucirumab plus docetaxel (3%) than with placebo plus docetaxel (11%), and there were no differences in quality of life between the two treatment arms.
Asked by ESMO to comment on the findings, Richard Cathomas, from Kantonsspital Graubünden in Chur, Switzerland, said: “This is the first trial to show a progression-free survival benefit compared to chemotherapy alone in patients with platinum-refractory urothelial cancer. However, the magnitude of benefit was 1.3 months and, while statistically significant, it raises the question of whether it is clinically relevant.
“We need to know if the improvement in progression-free survival translates into an overall survival benefit,” he noted, concluding that “it is too early for these results alone to change the standard of care second line treatment, which is immune checkpoint inhibition.”
But Cathomas added that “the improvement in response rate shows that ramucirumab does have an impact on the disease, so in future, angiogenesis inhibition may become part of the treatment armamentarium for urothelial cancer.”
The findings were published simultaneously in The Lancet.
By Laura Cowen
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