A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN)

285 Background: Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first line. Vinflunine is EMA approved and used in several European countries. Docetaxel is widely used in second line. Cabazitaxel is a taxane with clinical activity in docetaxel-refractory cancers. A randomised study was conducted to compare its efficacy vs vinflunine. Methods: This was a multicenter, randomised, open-label, phase II/III study, following a Simon’s optimal method with early stopping rules based on an interim futility analysis. The study (NCT01830231) was supported by a research grant from Sanofi. The trial was aiming at superiority of cabazitaxel compared to vinflunine in patients progressing to platinum. ECOG, anemia and liver metastases were stratification factors. The primary objective for the phase II study was overall response rate (ORR), and overall survival (OS) for the phase III. Secondary objectives included safety and progression free survival (PFS). Results: 70 patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Mean age 63 years; 56 (80%) were men. No statistically significant differences were detected between arms for ORR (p=0.26). Three patients (13%) obtained a partial response on cabazitazel (95% CI, 2.7–32.4) and six patients (30%) in the vinflunine arm (95% CI, 11.9–54.3). Median PFS for cabazitaxel was 1.9 months versus 2.9 months for vinflunine (p=0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for OS benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3-4 related adverse events were seen in 41% patients with no difference between arms. The most frequent toxicities associated with cabazitaxel were asthenia, diarrhea, anemia and febrile neutropenia. Conclusions: This phase II/III second line bladder trial comparing cabazitaxel with vinflunine was closed early when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those observed in the phase III. Clinical trial information: NCT01830231.