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HCC Armamentarium Expands, With Promising Agents on the Horizon

Brandon Scalea
Published: Tuesday, Mar 05, 2019

Aiwu Ruth He, MD, PhD

Aiwu Ruth He, MD, PhD

Several positive trials in advanced hepatocellular carcinoma (HCC) have led to an influx of available treatment options in a field that had become relatively stagnant, said Aiwu Ruth He, MD, PhD, and more promising agents are coming down the pike.

For more than a decade, sorafenib (Nexavar) was the only FDA-approved drug available for use in the advanced setting, but in the last 2 years, 5 additional agents have been added to the treatment armamentarium: lenvatinib (Lenvima), regorafenib (Stivarga), cabozantinib (Cabometyx), nivolumab (Opdivo), and pembrolizumab (Keytruda).

An agent of particular interest, pembrolizumab, was granted an accelerated approval by the FDA as a treatment for patients with HCC who were previously treated with sorafenib, based on positive data from the KEYNOTE-224 trial. However, in February 2019, Merck, the manufacturer of the drug, announced that the coprimary endpoints in its confirmatory trial, KEYNOTE-240, had not been met. Although single-agent pembrolizumab was found to improve overall survival (OS) compared with placebo, the difference in benefit was not considered to be statistically significant per the prespecified statistical plan (HR, 0.78; 95% CI, 0.611-0.998; P = .0238).1

Despite this, He said that the patients who respond to pembrolizumab do appear to experience clinical benefit from the therapy, though they account for a smaller subset of the overall population of patients with HCC. Therefore, investigators will need to identify a biomarker to determine which patients will benefit most from checkpoint inhibition.

Beyond pembrolizumab, there are other emerging agents in the space that He said possess ample potential. Data with ramucirumab (Cyramza) from the phase III REACH-2 trial, for example, have shown improved OS with the agent compared with placebo in patients with HCC who had previously received sorafenib and have alpha-fetoprotein concentrations of at least 400 ng/mL.2 Further, the combination of atezolizumab (Tecentriq) plus bevacizumab (Avastin) has shown promising antitumor activity in patients with advanced disease in early-phase trials.3

In an interview during the 2019 OncLive® State of the Science Summit™ on Gastrointestinal Cancers, He, an associate professor of medicine at Georgetown-Lombardi Comprehensive Cancer Center, discussed the newly crowded treatment landscape of HCC and highlighted next steps for research.

OncLive: What agents have entered the HCC treatment paradigm in recent years?

He: In the frontline setting, we have 2 TKIs: sorafenib and lenvatinib. Sorafenib was FDA approved in 2007. Lenvatinib was just approved last year, supported by data from the pivotal REFLECT trial. In the second-line setting, we now have 2 TKIs and 2 immune checkpoint inhibitors available. Regorafenib, a TKI, was approved by the FDA in 2017 for use in patients who have tolerated sorafenib and progressed on the drug. This [regulatory decision] was supported by positive data from the RESORCE trial. Cabozantinib was FDA approved in January 2019, based on results from the CELESTIAL trial.




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TitleExpiration DateCME Credits
Community Practice Connections™: Addressing Post-Transplant Obstacles: Current and Emerging Strategies to Evolve the Standard of Care for Patients With Graft-Versus-Host DiseaseMar 28, 20192.0
2017 Year in Review™: Clinical Impact of Immunotherapies in the Treatment of CancerMar 30, 20191.75
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