Phase III HEAT study adding lyso-thermosensitive liposomal doxorubicin to radiofrequency ablation in patients with unresectable hepatocellular carcinoma lesions

Won Young Tak, Shi Ming Lin, Yijun Wang, Jiasheng Zheng, Aldo Vecchione, Soo Young Park, Min Hua Chen, Stephen Wong, Ruocai Xu, Cheng Yuan Peng, Yi You Chiou, Guan Tarn Huang, Jianqiang Cai, Basri Johan Jeet Abdullah, June Sung Lee, Jae Young Lee, Jong Young Choi, Julieta Gopez-Cervantes, Morris Sherman, Richard S. FinnMasao Omata, Michael O'Neal, Lukas Makris, Nicholas Borys, Ronnie Poon, Riccardo Lencioni

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (d max ) of 3 to 7 cm. Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a d max of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy. Results: The primary endpoint was not met; in intention-totreat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin. Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes.

Original languageEnglish (US)
Pages (from-to)73-83
Number of pages11
JournalClinical Cancer Research
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tak, W. Y., Lin, S. M., Wang, Y., Zheng, J., Vecchione, A., Park, S. Y., Chen, M. H., Wong, S., Xu, R., Peng, C. Y., Chiou, Y. Y., Huang, G. T., Cai, J., Abdullah, B. J. J., Lee, J. S., Lee, J. Y., Choi, J. Y., Gopez-Cervantes, J., Sherman, M., ... Lencioni, R. (2018). Phase III HEAT study adding lyso-thermosensitive liposomal doxorubicin to radiofrequency ablation in patients with unresectable hepatocellular carcinoma lesions. Clinical Cancer Research, 24(1), 73-83. https://doi.org/10.1158/1078-0432.CCR-16-2433