Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma.

ABSTRACT: Background:Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out 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. Results:Minimum follow-up was 42?months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1?months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P?=?0.24]. In an exploratory assessment of OS, progression-free survival, 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, 0.38-0.94; P?=?0.03 (not adjusted for multiple subgroup analyses)], with corresponding 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. Conclusion:The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib. Trial Registration Number:NCT00704730.

SUBMITTER: Schlumberger M 

PROVIDER: S-EPMC5834040 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature