A randomized Phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN)
Bellmunt J (1,2), Kerst JM (3), Vázquez F (4), Morales-Barrera R (5), Grande E (6), Medina A (7), González Graguera M (8), Rubio G (9), Anido U (10), Fernández Calvo O (11), González-Billalabeitia E (12), Van den Eertwegh A (13), Pujol E (14), Perez-Gracia JL (15), González Larriba JL (16), Collado R (17), Los M (18), Maciá S 19, De Wit R (20); SOGUG and DUOS.
(1) Medical Oncology, Hospital del Mar-IMIM Barcelona, Barcelona, Spain.
(2) Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
(3) Netherlands Cancer Institute/AvL St Antonius Ziekenhuis, Nieuwegein, the Netherlands.
(4) Medical Oncology, Hospital General Universitario de Elche, Elche, Spain.
(5) Medical Oncology, Vall d´Hebron University Hospital, Vall d´ Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Spain.
(6) Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain.
(7) Medical Oncology, Centro Oncológico de Galicia, Galicia, Spain.
(8) Oncology, Hospital Son Llàtzer, Palma Di Mallorca, Spain.
(9) Medical Oncology, Fundación Jiménez Díaz, Madrid, Spain.
(10) Medical Oncology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
(11) Medical Oncology, Complejo Hospitalario Universitario Ourense, Orense, Spain.
(12) Medical Oncology, Hospital General Universitario Morales Meseguer-IMIB-UCAM, Murcia, Spain.
(13) Medical Oncology, VU University Medical Center, Amsterdam, Netherlands.
(14) Medical Oncology, Hospital Lozano Blesa, Zaragoza, Spain.
(15 Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
(16) Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain.
(17) Medical Oncology, Hospital San Pedro Alcántara, Cáceres, Spain.
(18) Internal Medicine, St. Antonius Ziekenhuis Hospital, Nieuwegein, Netherlands.
(19) Medical Department, Pivotal CRO, Madrid, Spain.
(20) Erasmus MC Cancer Institute, Rotterdam, Netherlands.
Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second line. Vinflunine is the only treatment approved in this setting by the European Medicines Agency (EMA) and taxanes are also widely used in second line.
Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy vs vinflunine.
PATIENTS AND METHODS:
This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II.
ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III.
Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI, 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI, 11.9-54.3). Median progression free survival 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 overall survival 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 the two arms.
This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously.Trial number: NCT01830231.
CITATION Ann Oncol. 2017 Apr 13. doi: 10.1093/annonc/mdx186