Ramucirumab improves progression-free survival in advanced urothelial cancer

Reuters Health Information: Ramucirumab improves progression-free survival in advanced urothelial cancer

Ramucirumab improves progression-free survival in advanced urothelial cancer

Last Updated: 2017-09-21

By Will Boggs MD

NEW YORK (Reuters Health) - Ramucirumab, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-2 signaling, combined with docetaxel, improves progression-free survival in patients with advanced or metastatic urothelial carcinoma that is refractory to platinum-based therapy, according to results from the phase 3 RANGE trial.

Platinum-based combination chemotherapy is first-line treatment for advanced or metastatic urothelial carcinoma, but the duration of response is limited and most patients become refractory. Immune-checkpoint inhibitors have shown clinical activity in this setting, but many patients have progressive disease as their best response.

Given favorable responses to ramucirumab plus docetaxel in a phase 2 study, Dr. Daniel P. Petrylak of Yale University School of Medicine and colleagues undertook a randomized phase 3 study of ramucirumab plus docetaxel versus placebo plus docetaxel in 530 patients with platinum-refractory advanced or metastatic urothelial carcinoma. Participants were from 124 centers in 23 countries.

By a median follow-up of 5.0 months, median progression-free survival was 4.07 months with ramucirumab plus docetaxel, significantly better than the 2.76 months with placebo plus docetaxel, according to the September 12 Lancet online report.

Estimated 12-month progression-free survival was 11.9% with ramucirumab and 4.5% with placebo, and the addition of ramucirumab to docetaxel improved progression-free survival across most subgroups.

A quarter of the ramucirumab group achieved objective responses (including 9 complete responses), compared with only 14% of placebo recipients (including 3 complete responses). Median durations of response were 5.65 and 4.17 months, respectively.

Quality of life and time to sustained deterioration in QOL did not differ between the treatment groups, nor did rates of adverse events and serious adverse events.

"Together, these phase 2 and phase 3 data suggest a favorable benefit-to-risk ratio for this combination treatment and might represent a new regimen for this patient population," the researchers conclude. But they also note that data on overall survival are yet forthcoming.

"While we wait for these data, results of the CALGB 90601 trial (NCT00942331) are awaited eagerly," writes Dr. Joaquim Bellmunt from Dana-Farber Cancer Institute, Boston, in a related editorial. "In that study, bevacizumab is being tested with chemotherapy in first-line treatment for urothelial cancer. Hopefully, in a situation similar to that reported with colorectal cancer, ramucirumab might improve outcomes after previous bevacizumab."

Dr. Melvin L.K. Chua from the National Cancer Centre Singapore, told Reuters Health by email, "This is a pivotal study, since it is the first trial showing efficacy of targeted therapy in this unfavorable subgroup of patients, who for the longest time lacked systemic options in the recurrence setting."

"However, this evidence comes in the era when immunotherapy has been shown to be effective in platinum-resistant and -sensitive urothelial cancers," he said. "It remains to be seen if immunotherapy is a better alternative versus ramucirumab and docetaxel, and thus why I feel this study may not be practice-changing."

Eli Lilly and Company sponsored the study, employed 6 of the 39 authors, and had various relationships with 14 other authors.

Dr. Petrylak did not respond to a request for comment.

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Lancet 2017.

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