medwireNews: Updated results from the RANGE trial support improved progression-free survival (PFS) with the addition of ramucirumab to docetaxel in patients with platinum-refractory advanced urothelial carcinoma, but show no significant overall survival (OS) benefit.
An earlier analysis of the phase III trial, presented at the ESMO 2017 congress in Madrid, and reported by medwireNews, found that the 263 individuals randomly assigned to receive intravenous ramucirumab 10 mg/kg followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle had a median PFS duration of 4.1 months.
This was significantly longer than the median of 2.8 months observed among the 267 patients who received placebo plus docetaxel.
In the current analysis, conducted after a median 7.4 months of follow-up, the median PFS was unchanged in both groups and the difference remained significant, with the stratified hazard ratio falling slightly from 0.76 to 0.70.
By contrast, there was no significant difference in OS between the patients who received the vascular endothelial growth factor receptor 2 antagonist and those who did not, at a median of 9.4 versus 7.9 months. There was also no significant OS difference between the two groups at 6, 9, 12, or 24 months.
Exploratory subgroup analyses indicated that patients receiving ramucirumab who had a primary tumor within the bladder had better OS than those receiving placebo, whereas there no difference between the two groups when the tumor was outside of the bladder.
In addition, the team observed a significant interaction between PD-L1 expression and OS, such that individuals with a PD-L1 combined positive score of 10 or higher had significantly longer OS with ramucirumab versus placebo, whereas those with lower PD-L1 expression levels did not.
The researchers note that the safety and quality of life outcomes in the current analysis were consistent with those previously reported.
Writing in The Lancet Oncology, Daniel Petrylak (Yale School of Medicine, New Haven, Connecticut, USA) and co-authors conclude: “Our results further support the progression-free survival benefit of the addition of an anti-vascular endothelial growth factor receptor 2 antibody to standard chemotherapy in this setting and represent, to our knowledge, the first positive randomised phase 3 data evaluating anti-angiogenic therapy in the treatment of patients with urothelial carcinoma.
“Appropriately designed trials testing the hypotheses derived from the results of subgroup and exploratory analyses in RANGE are warranted.”
In an accompanying comment, Yair Lotan, Xiaosong Meng, both from the University of Texas Southwestern Medical Center in Dallas, USA, point out that “[u]ntil recently, few salvage therapies were available” for patients with advanced, platinum-refractory urothelial cancer, but now several options, including ramucirumab, exist.
They describe this development as “encouraging” and conclude: “The resultant challenges rest with determining which patients are best served by which therapeutic options, the optimal sequence of treatments, and the potential for improved overall survival with combination treatments while minimising patient morbidity.”
And speaking at ESMO 2017, Petrylak told medwireNews that he believes that ramucirumab “should be used for those patients who really may not be eligible for checkpoint inhibition therapy or for those patients who have progressed on checkpoint inhibition therapy.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30668-0
Lancet Oncol 2019; doi: doi.org/10.1016/S1470-2045(19)30661-8