Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer

Toni K. Choueiri, Robert W. Ross, Susanna Jacobus, Ulka Vaishampayan, Evan Y. Yu, David I. Quinn, Noah M. Hahn, Thomas E. Hutson, Guru Sonpavde, Stephanie C. Morrissey, Geoffrey C. Buckle, William Y. Kim, Daniel P. Petrylak, Christopher W. Ryan, Mario A. Eisenberger, Amir Mortazavi, Glenn J. Bubley, Mary Ellen Taplin, Jonathan E. Rosenberg, Philip W. Kantoff

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Purpose: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. Patients and Methods: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m 2intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided - at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. Results: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. Conclusion: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.

Original languageEnglish (US)
Pages (from-to)507-512
Number of pages6
JournalJournal of Clinical Oncology
Volume30
Issue number5
DOIs
StatePublished - Feb 10 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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