Vinflunine maintenance therapy versus best supportive care after platinum combination in advanced bladder cancer: A phase II, randomized, open label, study (MAJA study, SOGUG 2011-02)—Interim analysis on safety.

Abstract

359 Background: Vinflunine (VFL) is a novel microtubule inhibitor currently approved by EMA as treatment after platinum progression, in metastasic bladder cancer. We evaluated whether maintenance vinflunine delays progression after response to CT. Methods: Multicenter, randomized, open label, proof-of-concept study that is being performed in 21 institutions members of the Spanish Oncology Genitourinary Group (SOGUG). Subjects are randomized to receive (arm A) VFL 320 mg/m2 (280mg/m2 for patients with PS=1, age ≥ 75 years, prior pelvic radiotherapy or creatinine clearance Cr <60ml/min) every 21 days plus best supportive care (BSC) vs. (arm B) BSC alone until disease progression. Main inclusion criteria: Subjects ≥18 and< 80 years of age with histological diagnosis of transitional cell carcinoma of the urothelial tract and measurable disease whith radiological response or stabilization after 4 to 6 cy of a cisplatin-containing doublet for metastasic/advanced disease (carboplatin allowed on cy 5-6). Primary objective: progression free survival (PFS). A sample size of 86 patients allocated in a 1:1 ratio is planned. Recruitment started on April 2012. A pharmacogenomic translational study will be conducted. Results: To September 2013, 46 pts have been enrolled, 20 in the VFL+BSC group, 26 in the BSC group. We present the results of the interim analysis including data from first 25 patients who have completed at least 2 cycles. Median age 65.6 years (range 54-77); PS 0/1, 44%/56%; CrCl <60 ml/min 16%; liver metastasis 16%; prior pelvic RT 8%. Primary tumour location: bladder 76%, upper urinary tract 20%, urethra 4%. Pure transitional cells 84%. Metastatic/locoregional disease, 72% / 28%. We analyzed 63 cy in the chemotherapy arm. Most common G3/4 (% cycles) AEs on vinflunine were constipation (12.7%), neutropenia (7.9%), fatigue (4.8%), myalgia (3.2%). One death was reported due to dyspnea, not related to the treatment. No febrile neutropenia was reported at the time of the analysis. Conclusions: Maintenance with vinflunine presented an acceptable security profile leading to trial continuation. Clinical trial information: 2011-001271-39.