A double-blind randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated advanced urothelial cancer.

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LBA239 Background: Vandetanib (V) is a novel small-molecule inhibitor that targets key signaling pathways in cancer including VEGF and EGF. V in combination with docetaxel (D) was assessed in patients (pts) who received prior platinum-based chemotherapy for advanced urothelial cancer (UC). Methods: Patients eligible for this randomized, multicenter, double-blind, investigator-initiated trial had metastatic UC after failure of prior platinum-based chemotherapy. Up to 3 prior therapies were allowed including paclitaxel. The primary objective was to determine whether once-daily oral V (100 mg) + D (75 mg/m2 IV q21 days) prolonged progression-free survival (PFS) vs. placebo (P) + D (80% power to detect 60% improvement in median PFS with 1-sided α=0.05). Patients on D+P, had the option to cross over to single agent V. Overall survival (OS), overall response rate (ORR), stable disease (SD), and safety were secondary objectives. Results: One-hundred and forty-two pts were enrolled at 16 institutions, 68% men; median age 65y; ECOG PS 0/1: 52%/48%; visceral involvement: 66%. 80% of patients had ECOG PS 1 and/or visceral metastases. 44% of patients had 2 or more prior systemic therapies and 15% had prior paclitaxel. Baseline characteristics were balanced in both arms. Median PFS was 11.1 weeks (wks) for D+V arm vs. 6.9 wks for D+P arm (HR=1.04, p=0.92). Median OS was 25.4 wks for the D+V arm vs. 30.6 wks for the D+P arm (HR 1.21, p=0.35). ORR was 7.1% for the D+V arm vs. 11.1% for the D+P arm (OR=0.6, 90% CI [0.2–1.6]). SD or better rates were 50.0% vs. 37.5% on D+V and D+P, respectively. As of December 2010, 5 pts were on therapy and 70% of pts died. Median follow-up for pts still alive is 7.2 months. Treatment-related grade >3 toxicities for D+V arm was 60% vs. 36% for the D+P arm (p=0.055) and were generally manageable (grade 4, 14% vs. 11%). Grade >3 toxicities that were more commonly seen in the D+V arm were rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%). Conclusions: 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. Toxicities were greater but manageable. [Table: see text]