By Charles Bankhead, Staff Writer, MedPage Today
Published: January 28, 2013
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
SAN FRANCISCO -- Outcomes in hepatocellular carcinoma (HCC) failed to improve after hepatic arterial embolization (HAE) with doxorubicin-eluting beads (LC Bead) versus beads without the drug (Bead Block), a randomized trial showed.
Patients treated with drug-free beads had an overall response rate of 11% compared with 6% of patients who received the drug-eluting beads. About 85% of patients in both arms had stable disease, reported Karen Brown, MD, reported Memorial Sloan-Kettering Cancer Center in New York City, and colleagues.
Progression-free survival (PFS) was slightly better with the beads alone, and HAE with the doxorubicin-containing beads led to a nonsignificant 3-month increase in overall survival (OS), said Brown at the Gastrointestinal Cancers Symposium.
"Doxorubicin-loaded drug-eluting beads did not improve response rate, median time to progression, progression-free survival, or overall survival in this randomized trial," she explained. "The addition of doxorubicin to the beads does not appear to increase toxicity or compromise safety."
"This study brings into question the added benefit of chemotherapy for embolization of hepatocellular carcinoma," she added.
HAE has established a role in the treatment of HCC, but chemoembolization has garnered more support among clinicians, largely without a complete understanding of the role chemotherapy might play in HAE.
Two studies published about a decade ago have provided the evidentiary basis for chemoembolization, Brown said. In particular, one study showed superior 1- and 2-year survival with chemoembolization versus embolization and conservative treatment in patients with unresectable HCC (Lancet 2002; 359: 1734-1739).
"There was a sequential design of the study that allowed for termination when there was a significant survival benefit demonstrated in either of the study arms [versus conservative care]," said Brown. "This occurred earlier in the transarterial chemoembolization group, so when the survival benefit was demonstrated in that group, the study was stopped."
She pointed out the the authors of that study acknowledged that there were not enough patients in the embolization group to draw definitive conclusions. "Nonetheless, over 10 years later, many people interpret this study as showing a survival benefit for transarterial chemoembolization compared with either embolization or best supportive care, which is not the case," she said.
Continuing with a comparative evaluation of the two HAE strategies, Brown's group recruited patients with Okuda stage I-II unresectable HCC and randomized them to embolization or to chemoembolization with beads containing 150 mg of doxorubicin.
The primary endpoint was objective response rate by RECIST criteria as determined from multiphase CT imaging performed 3 weeks after treatment. Disease progression or ≤5% tumor necrosis was considered treatment failure.
Secondary objectives included safety and tolerability, time to progression (TTP), PFS, OS, and an exploratory comparison of response and other outcomes between the two groups.
Data analysis included 92 patients. Brown reported five partial responses (11%) in the embolization group and three (6%) in the chemoembolization arm. Additionally, 40 (87%) patients in the embolization group had stable disease, as did 39 (85%) patients in the chemoembolization group.
Investigators also evaluated response by lesion, using European Association for Study of the Liver criteria. The analysis included 171 lesions. The results showed a 100% decrease in 58% of lesions with embolization versus 61% of lesions treated with chemoembolization.
The proportion of lesions that decreased in size by more than 50% were 24% with embolization and 27% with chemoembolization, and 17% versus 11% of lesions in the respective groups decreased by less than 50%. One lesion in each group increased in size by more than 20%.
Analysis of secondary endpoints showed no significant differences between the groups:
- 2-year probability TTP: 42% with embolization versus 49% with chemoembolization
- 2-year probability PFS: 11% versus 19%
- PFS: 5.2 months versus 4.6 months
- OS: 16.6 versus 19.6 months
Given current epidemiologic trends in HCC, the results have clear implications for management of the disease, said Françoise Mornex, MD, PhD, of Lyon University Hospital in France.
"The incidence of HCC is increasing everywhere in the world, so we need to find the best treatments and we need to optimize treatment," said Mornex, who was not involved in the study. "There are several methods to embolize and treat these patients, and we still don't know which is the best one, so this question is important, and these results in 100 patients are quite robust."
But she cautioned that questions still remain. "Should we reproduce these results with a larger cohort of patients? Should we believe in these results and change our practice directions? I'm not sure we should change our practice on the basis of one study, even if the study is very important," Mornex said.
Clinicians should consider the results and how they might fit into their own practice and then integrate the information as appropriate, she added.
Primary source: Gastrointestinal Cancers Symposium
Source reference:
Brown KT, et al "A randomized, single-blind, controlled trial of beads versus doxorubicin-eluting beads for arterial embolization of hepatocellular carcinoma (HCC)" GiCS 2013; Abstract 143.
http://www.medpagetoday.com/MeetingCoverage/MGICS/37038
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