A randomised Phase II trial of carboplatin and gemcitabine ± vandetanib in first‐line treatment of patients with advanced urothelial cell cancer not suitable to receive cisplatin

Abstract

Objectives To assess the efficacy and tolerability of the dual EGFR/VEGFR inhibitor, vandetanib, in combination with carboplatin and gemcitabine in the first line treatment of patients with advanced urolthelial cancer (UC) who were unsuitable for cisplatin. Patients and methods From 2011 and 2014, 82 patients were randomised from 16 hospitals across the UK into the TOUCAN double‐blind, placebo‐controlled randomised phase II receiving six 21‐day cycles of intravenous carboplatin (AUC 4.5 day 1) and gemcitabine (1000mg/m² days 1,8) in combination with either oral vandetanib 100mg or placebo (once daily). Progression‐free survival (PFS – primary endpoint), adverse events (AEs), tolerability and feasibility of use, objective response rate and overall survival (OS) were evaluated. Intention‐to‐treat and per protocol analyses were used to analyse the primary endpoint. Results Eighty‐two patients were randomised 1:1 to vandetanib (n=40) or placebo (n=42). 25 patients (30%) completed 6 cycles of all allocated treatment. Toxicity ≥grade 3 was experienced in 80% (n=32) and 76% (n=32) of patients on vandetanib and placebo arms respectively. Median PFS was 6.8 and 8.8 months for vandetanib and placebo arms, respectively (HR=1.07, 95% CI 0.65‐1.76, p=0.71); median OS was 10.8 vs 13.8 months (HR=1.41, 95% CI 0.79‐2.52, p=0.88); and radiological response rates were 50% and 55%. Conclusion There is no evidence that vandetanib improves clinical outcome in this setting. Our data do not support its adoption as the regimen of choice for first line treatment in UC patients who were unfit for cisplatin.