Ramucirumab Added to Docetaxel Extends PFS in Urothelial Carcinoma

The addition of ramucirumab to docetaxel improved progression-free survival (PFS) compared with docetaxel alone in a randomized phase II trial of patients with locally advanced or metastatic urothelial carcinoma. Adding icrucumab to docetaxel, however, did not improve PFS.

Docetaxel is not approved for treatment of urothelial carcinoma, but it is commonly used in North America as a palliative second-line treatment. “Outcomes are suboptimal, and a substantial unmet need persists to improve outcomes for patients with advanced urothelial carcinoma,” wrote study authors led by Daniel P. Petrylak, MD, of Yale School of Medicine in New Haven, Connecticut.

Agents that target the VEGF pathway could offer benefit in urothelial carcinoma, since the pathway is involved in tumor angiogenesis in this malignancy. The new trial compared docetaxel alone (45 patients), docetaxel plus ramucirumab (46 patients), and docetaxel plus icrucumab (49 patients.) The results were published online ahead of print in the Journal of Clinical Oncology.

The median PFS in the ramucirumab group was 5.4 months, compared with 2.8 months with docetaxel alone, for a hazard ratio of 0.389 (95% CI, 0.235–0.643; P = .0002). The icrucumab patients did not show benefit over docetaxel alone, at 1.6 months median PFS, for an HR of 0.863 (0.550–1.357; P = 0.5053).

Overall survival (OS) was no different between any of the groups. The median OS in the ramucirumab group was 10.4 months, compared with 9.2 months with docetaxel alone, for an HR of 0.733 (95% CI, 0.45–1.18; P = .201). The median OS with icrucumab was 6.7 months, also not significantly different.

More patients in the combination groups (83% with ramucirumab and 84% with icrucumab) experienced grade 3 or worse adverse events (AEs) than those in the docetaxel monotherapy group (67%). With ramucirumab, grade 3 or worse fatigue, febrile neutropenia, and anemia were more common than with docetaxel monotherapy. For icrucumab patients, fatigue, pulmonary embolism, and anemia were worse than docetaxel alone. Only 22% of docetaxel monotherapy patients had an AE leading to delay or modification of study drugs, compared with 50% of ramucirumab and 53% of icrucumab patients.

“Although multiple agents targeting the VEGF pathway have been evaluated in urothelial carcinoma, to our knowledge this is the first trial to demonstrate a PFS advantage in adding targeted therapy,” the study authors wrote. The ongoing phase III RANGE trial will provide further evidence regarding the combination of ramucirumab and docetaxel in locally advanced, unresectable, or metastatic urothelial carcinoma.