The present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin.
Patients with aUC, creatinine clearance 30-60 ml/min, performance status ≤1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days) or the control arm (carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days). Primary end-point was progression-free survival (PFS).
Sixty-two patients were randomised; a total of 59 patients were treated (29 VG, 30 CG). There was no significant difference in PFS between the treatment arms: median 6.2 months for VG versus 6.3 months for CG (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.44-1.28; P = 0.293). Median overall survival was 12.5 months for VG versus 10.6 months for CG. The overall response rate (ORR) was higher in the VG arm than in the CG arm (63% versus 40%) but was not statistically significant in the intention-to-treat analysis. Furthermore, VG showed a high complete response (CR) rate, 22% versus 3% in CG. In the per-protocol group, both ORR and CR were significantly higher for VG than for CG. The most common adverse events (AEs) were fatigue, haematological 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 combination of VG did not improve PFS compared with standard treatment with CG in patients unfit for cisplatin due to renal impairment. The response rate of VG indicates, however, an active regimen and warrants further studies. CLINICALTRIALS.
European journal of cancer (Oxford, England : 1990). 2019 Oct 21 [Epub ahead of print]
Karin Holmsten, Niels Viggo Jensen, Lene Sonne Mouritsen, Erika Jonsson, Camilla Mellnert, Mads Agerbæk, Cecilia Nilsson, Mette Moe, Andreas Carus, Elisabeth Öfverholm, Outi Lahdenperä, Yvonne Brandberg, Hemming Johansson, Mats Hellström, Hans von der Maase, Helle Pappot, Anders Ullén
PO Bäckencancer, Tema Cancer, Karolinska Universitetssjukhuset and Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: ., Department of Oncology, Odense Universitetshospital, Odense, Denmark., Department of Oncology, Herlev Gentofte Hospital, Herlev, Denmark., Department of Oncology, Norrlands Universitetssjukhus, Umeå, Sweden., Department of Oncology, Skånes Universitetssjukhus, Lund, Sweden., Department of Oncology, Aarhus Universitetshospital, Aarhus, Denmark., Department of Oncology, Västmanlands Sjukhus, Västerås, Sweden., Department of Oncology, Aalborg Universitetshospital, Aalborg, Denmark., Department of Oncology, Sahlgrenska Universitetssjukhuset, Göteborg, Sweden., Department of Oncology, Åbo Universitetscentralsjukhus, Åbo, Finland., PO Bäckencancer, Tema Cancer, Karolinska Universitetssjukhuset and Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Department of Oncology, Rigshospitalet, Copenhagen, Denmark.