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Expert Provides Clarity on Treatment of Advanced HCC

Angelica Welch
Published: Thursday, Jun 28, 2018

Mitesh J. Borad, MD

Mitesh J. Borad, MD

Although hepatocellular carcinoma is less frequent in the United States with less than 40,000 cases per year, the global incidence per year is estimated to be 782,000 cases, said Mitesh J. Borad, MD.

In a presentation during the 2018 OncLive® State of the Science Summit™ on Gastrointestinal Cancers, Borad, an associate professor of medicine in the Division of Hematology/Oncology at Mayo Clinic, discussed liver-directed therapies, systemic therapy, and the management of liver cancer.

HCC is the most common primary cancer of the liver; typical etiologies for HCC include hepatitis B or C, metabolic syndrome, and alcoholic liver disease.

“This is a dual disease,” said Borad. “You are not only dealing with the tumor, but the background in which it arises such as cirrhosis or fibrosis—which can drive outcomes in patients. Both things really need to be considered.”

Borad says that patients can be broadly categorized into 3 stages: early-, intermediate-, and advanced-stage disease. In early-stage disease, surgery or transplant is a viable option, and in intermediate- and advanced-stage disease, locoregional therapy or systemic therapy should be considered.

Liver-Directed Therapies

Liver-directed therapies include embolization, radiofrequency ablation, cryoablation, radioembolization, alcohol ablation, and external beam radiation.

The SARAH study evaluated the safety and efficacy of selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) resin microspheres compared with sorafenib (Nexavar) in patients with locally advanced and inoperable HCC. The results of this randomized phase III trial did not show significant differences in outcomes in overall survival (OS); OS for patients who received SIRT was 8.0 versus 9.9 months with sorafenib (P = .179).1 Responses were somewhat higher in the radioembolization arm, says Borad, but that did not translate into survival advantage.

SIRveNIB was an Asian-Pacific study with a similar question as SARAH: Can patients do better with sorafenib? Almost 500 patients with advanced-stage HCC were treated with either SIRT or sorafenib. This was also considered a negative study, with similar results in both arms. Although there was a higher tumor response rate with SIRT, Borad said that unless these responses translate into survival differences, they are not impactful in the advanced setting.

Borad said that the take-home message from these 2 studies is that Y-90 remains a reasonable modality to treat HCC, despite the negative studies. Future studies should focus on liver-limited cases and earlier-stage disease to potentially optimize the use of Y-90.

Systemic Therapy

In the first-line setting, patients with advanced HCC should be treated systemically with either sorafenib or lenvatinib (Lenvima), Borad says.

Sorafenib was the rst FDA-approved systemic therapy for the treatment of patients with HCC, and up until recently, it was the only agents to show a significant improvement in OS in this field. This approval was based on results from the SHARP study.

The phase III REFLECT study, updated results of which were presented at the 11th Annual Conference of the International Liver Cancer Association, compared lenvatinib versus sorafenib in the first-line setting. The median OS with lenvatinib was 13.6 versus 12.3 months for sorafenib, and there was an improvement in progression-free survival (PFS) by 3.7 months compared with sorafenib.2 In the 954-patient study, median PFS with lenvatinib was 7.4 versus 3.7 months with sorafenib (HR, 0.66; 95% CI, 0.57-0.77; P <.00001).

A supplemental new drug application for lenvatinib in this setting has been accepted by the FDA. Under the Prescription Drug User Fee Act, the agency will decide on the approval by August 24, 2018. “While downstaging is generally not a major objective in advanced disease in patients, higher response rates with lenvatinib are provocative and should be studied in a formal prospective study in borderline resectable patients,” said Borad.

Borad concluded that either of these options are viable, but the hand-foot toxicities with sorafenib are dreaded by most patients and physicians. Although sorafenib might become generic in the near future, so that may be a factor in terms of cost, he adds.

In the second-line setting, there are more options for treatment. There are 2 antiangiogenics, regorafenib (Stivarga) and cabozantinib (Cabometyx), as well as the PD-1 inhibitor nivolumab (Opdivo).

In April 2017, the FDA approved regorafenib as a second-line treatment for patients with HCC who have previously received sorafenib. This approval was based off findings from the phase III RESORCE trial, which evaluated the safety and efficacy of regorafenib versus placebo in patients with HCC who had progressed on sorafenib.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Individualizing Treatment After Second-Line Therapy for Patients With mCRCAug 29, 20191.0
Community Practice Connections™: Navigating New Sequencing Challenges for the Treatment of Hepatocellular CarcinomaAug 30, 20191.5
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