Annals of oncology : official journal of the European Society for Medical Oncology 2017 09 22() doi 10.1093/annonc/mdx479
Primary analysis of the double-blind, phase 3 EXAM trial demonstrated significant improvement in progression-free survival (PFS) with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was performed after long-term follow-up.
Patients and Methods
EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported.
Minimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 v 21.1 months), although the difference did not reach statistical significance (stratified hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.64 to 1.12; P = 0.24). In an exploratory assessment of OS, PFS, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo (HR, 0.60; 95% CI, 0.38 to 0.94; P = 0.03 [not adjusted for multiple subgroup analyses]), with correspoding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis.
The secondary endpoint was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically non-significant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib.
Trial Registration Number