Maintenance Vinflunine Extends PFS in Advanced Urothelial Carcinoma

Maintenance therapy with vinflunine yielded longer progression-free survival (PFS) compared with best supportive care in patients with advanced urothelial carcinoma who achieved disease control with chemotherapy, according to a new study.

Most patients with urothelial carcinoma respond to chemotherapy, but the duration of response is limited and prognosis after progression is poor. “An attractive approach might be to introduce maintenance therapy after first-line treatment in patients who achieve disease control,” wrote study authors led by Joaquim Bellmunt, MD, PhD, of Dana-Farber/Brigham and Women’s Cancer Center in Boston. “Vinflunine is a potentially suitable agent for maintenance therapy because its toxicity profile is favorable and without cumulative effects.”

The researchers conducted a randomized, open-label, phase II study including 88 patients across 21 hospitals in Spain. Patients had locally advanced, surgically unresectable, or metastatic urothelial carcinoma, and had achieved disease control after treatment with cisplatin and gemcitabine. Of those, 45 patients received vinflunine maintenance therapy every 21 days, and 43 received best supportive care; 1 patient from the vinflunine group was lost to follow-up immediately after randomization. The results of the analysis were published in Lancet Oncology.

Patients were followed for a median of 15.6 months; those alive at data cutoff were followed for a median of 27.6 months. Of the 44 vinflunine patients, 29 (66%) had progressive disease and 24 (55%) had died; in the supportive care group, 36 patients (84%) had progressive disease and 32 (74%) had died.

The median PFS was 6.5 months with maintenance therapy compared with 4.2 months with best supportive care, for a hazard ratio of 0.59 (95% CI, 0.37–0.96; P = .031). That difference remained significant when patients with locoregional disease were excluded, but it disappeared when those with liver metastases were excluded.

The median overall survival was 16.7 months with vinflunine and 13.2 months without it; these data remain immature and will be reanalyzed after a median follow-up of at least 24 months.

There was an interim safety analysis performed, which deemed the toxicity acceptable, allowing the study to continue. The most common grade 3 or 4 hematologic adverse event with vinflunine was neutropenia (18% vs none in supportive care group). For grade 3/4 nonhematologic adverse events, the most common included asthenia and constipation. Seven patients required a vinflunine dose reduction, and treatment was discontinued due to drug-related events in three patients (7%).

The authors noted that vinflunine is not registered outside of Europe and thus these results may be difficult to generalize elsewhere. Still, they wrote that “further studies are warranted to better establish the role of vinflunine in maintenance therapy, including combinations with checkpoint inhibitors.”