A Randomized Phase II Trial of Vinflunine and Gemcitabine Versus Carboplatin and Gemcitabine in Cisplatin-Ineligible Patients with Advanced Urothelial Carcinoma - Expert Commentary

A significant number of patients with locally advanced and metastatic urothelial cancer (aUC) are not eligible for cisplatin-based chemotherapy.

A paper published by Holmsten et al. in the European Journal of Cancer compared the efficacy vinflunine and gemcitabine combination versus vinflunine and carboplatin combination as first-line therapy for advanced urothelial carcinoma (aUC) patients who are unfit for cisplatin due to renal impairment.1 In this randomized multi-center Phase II trial (VINGEM), the investigators included 59 patients who didn’t receive prior chemotherapy and have impaired renal function and performance status £1 into two groups. The experimental arm (VG) included 29 patients who received vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days and the control arm (CG) that included 30 patients who received carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days. 

The investigators found no significant differences in progression-free survival between VG 6.2 months and CG 6.3 months. Similarly, overall survival was not significantly different between the VG group (12.5 months) and the CG group (10.7 months. The overall response rate (ORR) was higher in the VG group (63%) in comparison to the CG group (40%) but this difference was not statistically significant in the intention-to-treat analysis. The VG group had a higher complete response (CR) rate (22%) in comparison to the CG group (3%) in the per-protocol analysis. The most common adverse events (AEs) were fatigue, hematological toxicities, gastrointestinal disorders, and nausea/vomiting. Common grade III/IV AEs were neutropenia (VG 62%, CG 43%), thrombocytopenia (VG 7%, CG 37%) and febrile neutropenia (VG 31%, CG 7%).

The study found no significant differences between the two regimens but highlights the activity of the VG regimen in cisplatin-ineligible patients. While cisplatin-ineligible aUC patients with high PDL1 expression can benefit from immune checkpoint inhibition, cisplatin-ineligible patients with low PDL1 expression need additional treatment options.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


1. Holmsten, Karin, Niels Viggo Jensen, Lene Sonne Mouritsen, Erika Jonsson, Camilla Mellnert, Mads Agerbæk, Cecilia Nilsson et al. "Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM)." European Journal of Cancer (2019).

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