San Francisco, CA—Less proved to be the equivalent of more in a randomized comparison of empty versus chemotherapy-filled embolization beads for the treatment of patients with hepatocellular carcinoma (HCC), as shown in the results of a randomized study presented at the 2013 Gastrointestinal Cancers Symposium.
Treatment with the beads alone led to an overall response rate of 11% compared with 6% for patients who underwent hepatic arterial embolization with doxorubicin (Adriamycin)-eluting beads. A similar proportion of patients in each treatment arm reached stable disease.
Progression-free survival (PFS) favored the drug-free beads, whereas chemoembolization had a small advantage in overall survival (OS). Neither of the differences achieved statistical significance, reported Karen T. Brown, MD, FSIR, interventional radiologist in the Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York.
“This study brings into question the added benefit of chemotherapy for embolization of hepatocellular carcinoma,” said Dr Brown.
Chemoembolization has an established role in the treatment of HCC, despite a paucity of evidence to support its use. According to Dr Brown, the rationale for the intervention rests largely on the results of 2 clinical studies, which were published approximately a decade ago, that suggested a survival advantage for chemoembolization versus embolization alone.
One of the trials compared embolization and chemoembolization with conservative therapy. The trial design called for termination when either intervention achieved a significant advantage versus conservative care. The difference occurred earlier in the chemoembolization arm, but that did not mean that the drug-eluting beads were superior to the empty beads, which the investigators acknowledged.
“Over 10 years later, many people still interpret this study as showing a survival benefit for transarterial chemoembolization compared with embolization or best supportive care, and that is not the case,” Dr Brown said.
In this new study, the investigators randomized patients with Okuda stage I or stage II unresectable HCC to chemoembolization with doxorubicin or to embolization with the beads alone. The primary end point was an objective response rate, which was determined by computed tomography 3 weeks after treatment.
Of the 92 patients, 5 in the embolization arm and 3 in the chemoembolization arm met the Response Evaluation Criteria in Solid Tumors, Dr Brown reported. Another 40 (87%) patients achieved stable disease with the drug-free beads, as did 39 (85%) patients in the chemoembolization group.
The response by individual lesions showed that 58% of the lesions had a 100% decline in size in the embolization arm versus 61% in the chemoembolization group. Approximately 25% of the lesions in each group decreased by 50%. A single lesion in each arm increased in size by >20%.
The PFS was 5.2 months with the drug-free beads and 4.6 months with the doxorubicin-containing beads. OS was 16.6 months versus 19.6 months, respectively, favoring chemoembolization, but not significantly.
Adverse events and serious adverse events occurred in a similar proportion of patients in the 2 groups.
The results provide “robust” evidence of the equivalence of the 2 treatment strategies, but they do not resolve all of the issues related to hepatic arterial embolization for the treatment of patients with HCC, said Françoise Mornex, MD, PhD, Head of the Department of Radiation Oncology, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. The outcome of the study does not exclude potential benefits from other embolization strategies. Moreover, the robust evidence came from a study involving fewer than 100 patients, so the need for a larger trial remains unclear, Dr Mornex concluded.