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Ramucirumab Plus Docetaxel Extend PFS For Advanced Urothelial Cancer

RANGE results support the use of ramucirumab alongside docetaxel for platinum-refractory urothelial carcinoma
20 Nov 2019
Anticancer Agents;  Therapy;  Urothelial Cancers

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Results for the RANGE trial have been updated, confirming a significant gain in progression-free survival (PFS) for patients with locally advanced or metastatic platinum-refractory urothelial carcinoma with the use of ramucirumab alongside docetaxel. 

“Our results further support the progression-free survival benefit of the addition of an anti-vascular endothelial growth factor receptor 2 [VEGFR2] 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”, say Daniel Petrylak, from Yale University in New Haven, Connecticut, USA, and co-investigators. 

After a median of 7.4 months, the primary endpoint of median PFS was 4.1 months for the 263 patients randomly assigned to receive a 21-day cycle of ramucirumab 10 mg/kg followed by docetaxel 60 or 75 mg/m2 dependent on location versus 2.8 months for the 267 patients who were instead given placebo plus docetaxel. This gave a significant a hazard ratio (HR) of 0.696, revised from the previously reported preliminary HR of 0.757. 

The PFS benefit included significantly higher rates of PFS with ramucirumab therapy in landmark analyses performed at 3, 6, 9 and 12 months of follow-up, the authors report in The Lancet Oncology. 

However, overall survival (OS) did not significantly differ between the two treatment arms, at a median of 9.4 months with ramucirumab plus docetaxel and 7.9 months for placebo plus docetaxel. And analysis failed to identify any patient subgroups that derived a significant OS benefit from ramucirumab therapy. 

Nevertheless, prespecified exploratory analysis indicated that patients with a PD-L1 combined positive score of 10 or above had significantly longer PFS and OS with ramucirumab than placebo, whereas no such benefit with ramucirumab was detected for those with a score of less than 10. 

“Appropriately designed trials testing the hypotheses derived from the results of subgroup and exploratory analyses in RANGE are warranted”, suggest Daniel Petrylak et al.  

Ramucirumab plus docetaxel was associated with a higher rate of grade 3 or more severe treatment-emergent adverse events than placebo plus docetaxel (48 vs 41%). Events that were slightly more common with ramucirumab included febrile neutropenia (9 vs 6%) and neutropenia (6 vs 2%) and the rate of serious events was comparable (43 vs 40%). 

The authors of an accompanying comment note that the “small window for treatment of metastatic urothelial carcinoma” means that most patients will not survive long enough to cycle through all available therapies, as demonstrated in the RANGE trial where only 27% of participants went on to receive further treatment after the study regimen. 

Commentators Yair Lotan and Xiaosong Meng, from the University of Texas Southwestern Medical Center in Dallas, USA, note that five checkpoint inhibitors have been approved by the US FDA for metastatic urothelial carcinoma but only pembrolizumab has shown a survival benefit versus chemotherapy in phase III trials, while the FGFR inhibitor erdafitinib has been approved for patients with a relevant mutation.  

“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 minimizing patient morbidity”, they conclude. 

 

References 

Last update: 20 Nov 2019

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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