A randomized phase II/III trial of a tumor vascular disrupting agent fosbretabulin tromethamine (CA4P) with carboplatin (C) and paclitaxel (P) in anaplastic thyroid cancer (ATC): Final survival analysis for the FACT trial.

Abstract

5502 Background: CA4P, a vascular disrupting agent (VDA), has shown clinical activity as monotherapy in patients with ATC. Results include a durable CR in a phase I trial and a median survival of 4.7 months with 34% of patients alive at 6 months and 23% of patients alive at 1-year in a Phase 2 trial. Interim results previously presented from this phase II/III study evaluating CA4P in combination with carboplatin (C) + paclitaxel (P) in patients with ATC suggested a survival benefit with the combination therapy. Final survival and safety data are now available. Methods: This is a multicenter, open-label, 2:1 randomized trial for patients with histologically confirmed ATC. 80 out of 180 planned patients were randomized to receive up to 6 cycles of C + P with CA4P (CA4P Arm) or without CA4P (Control Arm). The targeted sample size of 180 patients was not reached due to slow enrollment. After 6 cycles of therapy, patients on the CA4P Arm without progression could continue to receive CA4P until disease progression. The primary objective of this study is overall survival (OS). Secondary objectives include safety, 1-year survival, and progression-free survival. Results: 75 of the 80 randomized patients received treatment with a median (min, max) follow up of 4.7 (0.1, 32.6) months. All deaths have been due to disease progression except 2 patients whose deaths were attributed to disease related complications. The median survival time for the CA4P Arm was 5.2 months vs. 4.0 months for the Control Arm (hazard ratio and 95% CI of 0.65 [0.38, 1.10]) from the intent-to-treat analysis. This would suggest a 35% reduction in the risk of death. One year survival was 27% on the CA4P Arm vs. 9% on the Control Arm (p =0.065, Fisher’s Exact Test). Grade 1-2 hypertension and Grade 3-4 neutropenia were more common on the CA4P Arm. Conclusions: This trial, the largest prospective randomized trial ever conducted in ATC, suggests that CA4P improves OS with a tripling of 1-year survival. The regimen continues to be well-tolerated, with AEs and deaths primarily related to ATC and disease progression.