Analysis of a 285-patient subgroup treated with ThermoDox plus radiofrequency ablation shows a statistically significant 59% improvement in overall survival when compared to patients who were treated with optimised radiofrequency ablation alone.
Celsion has announced updated results from its retrospective analysis of the 701-patient HEAT study (Hepatocellular carcinoma study of RFA and ThermoDox) of ThermoDox, the proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radiofrequency ablation in hepatocellular carcinoma. HEAT was an international, multicentre, randomised, placebo-controlled study that did not meet its primary endpoint to show sufficient evidence of clinical effectiveness of ThermoDox.
The latest quarterly overall survival analysis in January 2015 demonstrated that in a large, well-bounded, subgroup of patients (n=285, 41% of the study patients), the combination of ThermoDox and optimised radiofrequency ablation provided a 59% improvement in overall survival compared to optimised radiofrequency ablation alone. The hazard ratio at this analysis is 0.628 (95% CI 0.420–0.939) with a p-value of 0.02.
“The consistency of the data from the HEAT Study over the past two years is quite compelling, demonstrating the significant potential for ThermoDox in combination with an optimised radiofrequency ablation regimen to markedly improve overall survival in primary liver cancer patients,” stated Riccardo Lencioni, professor and director, Diagnostic Imaging and Intervention, Pisa University School of Medicine, Italy. “These findings provide a strong rationale for the ongoing OPTIMA Study and may also underscore the interest of clinical investigators to evaluate the potential of ThermoDox plus optimised radiofrequency ablation for curative intent among intermediate stage hepatocellular carcinoma patients.”
The data from the most recent quarterly HEAT Study post-hoc analysis continued to strongly suggest that ThermoDox may significantly improve overall survival compared to a radiofrequency ablation control in patients whose lesions undergo optimised radiofrequency ablation treatment for 45 minutes or more. These findings apply to patients with single hepatocellular carcinoma lesions (64.4% of the HEAT Study population) from both size cohorts of the HEAT Study (3–5cm and 5–7cm) and represent a subgroup of 285 patients.
Michael H Tardugno, Celsion’s chairman, president and chief executive officer said: “The lessons learned from the HEAT study together with prospective supportive preclinical study results formed the basis for our global Phase III OPTIMA study evaluating ThermoDox in combination with a standardised radiofrequency ablation protocol in primary liver cancer, and we look forward to sharing this latest data update with our investigators worldwide as we continue to advance this programme.”
The phase III OPTIMA study is expected to enrol up to 550 patients globally in up to 100 clinical sites in the USA, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimised radiofrequency ablation, which will be standardised to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimetres, vs. standardised RFA alone. The primary endpoint for the trial is overall survival, which is supported by post-hoc analysis of data from the company’s 701 patient HEAT Study, where optimised radiofrequency ablation has demonstrated the potential to significantly improve survival when combined with ThermoDox. The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC).
