Spanish Trial Shows Benefit of Vinflunine Maintenance in Advanced Urothelial Carcinoma
In a Spanish phase II trial reported in The Lancet Oncology, García-Donas et al found that maintenance therapy with vinflunine improved progression-free survival vs best supportive care alone in patients with advanced urothelial carcinoma with disease control on first-line chemotherapy.
Study Details
In the open-label trial, 87 evaluable patients from 21 sites in Spain with locally advanced, surgically unresectable or metastatic transitional cell carcinoma of the urothelial tract and disease control after 4 to 6 cycles of cisplatin and gemcitabine (carboplatin allowed after cycle 4) were randomized between April 2012 and January 2015 to receive vinflunine plus best supportive care (n = 44) or best supportive care alone (n = 43). Vinflunine was given every 21 days via 20-minute infusion at 320 mg/m² or 280 mg/m² in patients with an Eastern Cooperative Oncology Group performance status of 1, age ≥ 75 years, previous pelvic radiotherapy, or creatinine clearance < 60 mL/min. The primary endpoint was median progression-free survival longer than 5.3 months in the vinflunine group.
Outcomes
Median follow-up was 15.6 months. In the vinflunine group, disease progression occurred in 29 patients (66%) and death in 24 patients (55%), compared with 36 (84%) and 32 patients (74%) in the best supportive care group. Median progression-free survival was 6.5 months (95% confidence interval [CI = 2.0–11.1 months) in the vinflunine group vs 4.2 months (95% CI = 2.1–6.3 months) in the best supportive care group (hazard ratio = 0.59, P = .031). Overall survival data are immature. At the time of analysis, median overall survival was 16.7 months vs 13.2 months.
Adverse Events
The most common grade 3 or 4 adverse events in the vinflunine group were neutropenia (18% vs 0% in best supportive care group), asthenia/fatigue (16% vs 2%), and constipation (14% vs 0%). Eighteen serious adverse events were reported in the vinflunine group and 14, in the best supportive care group, with the most common in the vinflunine group consisting of constipation (5%), paralytic ileus (2%), and incarcerated hernia (2%). One patient in the vinflunine group died of treatment-related pneumonia.
The investigators concluded: “In patients with disease control after first-line chemotherapy, progression-free survival exceeded the acceptable threshold with vinflunine maintenance therapy. Moreover, progression-free survival was longer with vinflunine maintenance therapy than with best supportive care. Vinflunine maintenance had an acceptable safety profile. Further studies of the role of vinflunine are warranted.”
The study was funded by Pierre-Fabre Médicament.
Joaquim Bellmunt, MD, of Dana-Farber/Brigham and Women’s Cancer Center, is the corresponding author of The Lancet Oncology article.
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