A post-hoc analysis of results from the phase III HEAT Study of ThermoDox, a heat-activated liposomal encapsulation of doxorubicin in combination with radio frequency ablation, suggests the agent may significantly improve overall survival in primary liver cancer patients that receive RFA treatment for 45 minutes or more.
This analysis followed the announcement on January 31, 2013, that the HEAT Study did not meet its primary endpoint of progression-free survival.
As provided for in the HEAT Study’s Special Protocol Assessment agreement with FDA, the drug’s sponsor, Celsion Corporation, continues to follow patients for overall survival. Data from four quarterly reviews of overall survival have been evaluated since the announcement of top-line PFS data.
These findings apply to patients with single HCC lesions, 64.4 percent of the HEAT Study population, from both size cohorts of the HEAT Study (3-5 cm and 5-7 cm) and represent a subgroup of 285 patients, or 41 percent of the patients in the HEAT Study.
In the patient subgroup treated in the ThermoDox arm whose RFA procedure lasted longer than 45 minutes (n=285, or 63 percent of single lesion patients), clinical results indicate a 55 percent improvement in overall survival (HR=0.64; 95% CI: 0.41-1.00; p=0.0495). Median overall survival for this subgroup has not yet been reached.
In contrast, the patient subgroup treated with ThermoDox whose RFA procedure lasted less than 45 minutes in duration (n=167, or 37 percent of single lesion patients) indicated a Hazard Ratio of 1.12 (95% CI 0.68 – 1.86) and a P-value = 0.66. Median overall survival for this subgroup has not yet been reached.
The hazard ratios reported above warrant additional clinical development, and should be viewed with caution since they are based on a retrospective analysis and the HEAT Study has not reached its median point for overall survival analysis.
Celsion will continue to follow patients in the HEAT Study to the secondary endpoint, overall survival, and will update the subgroup analysis based on RFA heating duration. Celsion anticipates initiating a global phase III trial in the first half of 2014.
