Should TACE and External Beam Radiotherapy Become a New Standard for Locally Advanced Hepatocellular Carcinoma With Macroscopic Vascular Invasion?

For patients with locally advanced hepatocellular carcinoma (HCC) with macroscopic vascular invasion, sorafenib is the only evidence-based treatment option. However, responses to sorafenib are typically poor in this population, and sorafenib offers only a 47-day improvement in survival compared to placebo. External beam radiotherapy (RT) is a potentially attractive treatment option for patients with locally advanced HCC, and combinations of RT with transarterial chemoembolization (TACE) have demonstrated promise in observational studies in patients with HCC with macroscopic vascular invasion.

In a prospective, randomized, open-label clinical trial (N = 90), the efficacy of serial TACE and early RT (began within 3 weeks after first TACE) was compared to sorafenib in treatment-naïve patients with liver-confined HCC showing macroscopic vascular invasion. TACE-RT was associated with a significant improvement in progression-free survival (PFS) at 12 weeks compared to sorafenib (86.7% vs 34.3%; P<.001), the primary endpoint of the study. The 24-week PFS rate was 55.6% with TACE-RT versus 7.4% with sorafenib (P<.001), and median time to progression was 31 weeks with TACE-RT, compared to 11.7 weeks with sorafenib (P<.001). The radiologic response rate was also improved, from 2.2% with sorafenib to 33.3% with TACE-RT (P<.001). Furthermore, TACE-RT significantly improved overall survival (OS) compared to sorafenib (55 weeks vs 43 weeks; P = .04).

Adverse events (AEs) of any grade occurred in 91.1% of patients receiving TACE-RT and 93.2% of patients receiving sorafenib. Serious AEs occurred in 5 patients in each group.

The investigators concluded that TACE-RT offers a safe and effective alternative to sorafenib in patients with HCC with macroscopic vascular invasion, with significant improvements in both response rate and survival. Authors of an accompanying commentary called the results seen with TACE-RT impressive, and indicated that this treatment strategy may provide a much needed survival boost for patients with HCC with macroscopic vascular invasion. However, they cautioned that these data are not sufficient to support incorporating this treatment approach into clinical practice, particularly due to the small sample size, lack of information on cirrhosis, and imbalance between patients with hepatitis B virus and Hepatitis C virus-related liver disease. The majority of the patients (84.4%) in the trial had hepatitis B virus-related liver disease, which potentially has less favorable outcomes with sorafenib than hepatits C virus-related HCC. In addition, the median time to progression with sorafenib was shorter than reported in other trials. ‘’Work in this realm is just beginning’’, said the authors, pointing on the need for additional prospective studies to validate and optimize these findings in other patient populations.

JAMA Oncol. 2018 March 15 [Epub ahead of print].

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