Expert Explores Emerging Role of Personalized Medicine in HCC Treatment

Fabio Piscaglia, MD

Updates to the European Association for the Study of the Liver (EASL) clinical guidelines introduce more opportunities for individual patient management of hepatocellular carcinoma (HCC), explained Fabio Piscaglia, MD.

The 2018 updated guidelines, which were presented during the 12th International Liver Cancer Association (ILCA) Annual Conference in London, United Kingdom, were designed to have a more tailored HCC management approach; however, precision medicine in HCC has not been fully achieved, said Piscaglia, associate professor in the Department of Medical and Surgical Sciences at the Universitá di Bologna, in Bologna, Italy. Piscaglia presented the EASL guideline updates during the meeting.¹

Specifically, the refinements include an endorsement to conduct biopsies in lesions that meet standard HCC criteria at imaging, modified and individualized treatment decisions by a treatment allocation flowchart; and broader eligibility for liver resection, which includes compensated Child-Pugh class A liver function with Model for End-stage Liver Disease score.

In an interview with OncLive, Piscaglia discussed how the updated guidelines are facilitating better use of personalized medicine, and how precision medicine could eventually improve the treatment landscape.

HCC is a bit behind other tumor types in terms of developing a precision medicine approach “because we have not [had] much tissue material to gain more information,” said Piscaglia, adding it is because HCC arises in the background of liver cirrhosis.

“These patients need tailored treatment, but today, there are no molecular signatures, and no biomarkers able to deliver [precision] treatment,” said Piscaglia.

However, the new EASL guidelines, he said, do make substantial progress toward personalized medicine, such as with surveillance. EASL strongly recommended an improvement in the implementation of screening programs to identify at-risk patient populations. Moreover, patients at high risk of developing HCC should be entered into surveillance programs.

While patient selection for resection once depended on the degree of portal hypertension, the new guidelines take a refined approach and consider not only portal hypertension but the amount of liver to be sacrificed, the location of the tumor, liver function, and the type of surgery offered to the patient. The guidelines also offer a left-to-right stage migration—which allocates patients to the next appropriate therapy—and a right-to-left direction, in which more aggressive treatment is offered after having achieved a consensus at a multidisciplinary tumor board.

Regarding the guidelines, Piscaglia said that his takeaway message is 2-fold—first, that it is critical to establish the correct diagnosis without delay.

“There is a trend not to be properly aggressive in obtaining tissue sample in biopsy,” he said, adding that many clinicians prefer a watch-and-wait approach to a nodule that does not seem to be cancerous. Previously, this was an understandable approach when sorafenib (Nexavar) was the sole FDA-approved systemic therapy, he explained.

Second, however, given that new treatments have been approved by the FDA, such as frontline lenvatinib (Lenvatinib), and second-line nivolumab (Opdivo) and regorafenib (Stivarga), patients should be offered such therapies once locoregional therapies fail.

“We should not be afraid of starting pharmacological treatment early,” said Piscaglia, noting that a patient who is successfully treated on these agents may potentially return to locoregional therapy.

Piscaglia is also awaiting results of the CheckMate-459 trial, which compares frontline treatment with nivolumab with sorafenib (NCT02576509).

“This will be one of the most important [studies] for the future of our patients,” he said.

In looking to the future of systemic therapy, as well as the future of precision medicine for HCC, Piscaglia said that he is eagerly following the recently announced phase III results from the REACH-2 trial. Results of the study showed that patients with high alpha-fetoprotein had improved overall survival with ramucirumab versus placebo.²

“This will probably be the first piece of precision medicine; this will be the first step on which we can decide whether 1 patient can receive one or the other drug based on a biomarker,” said Piscaglia.

For example, biomarkers will be critical to understanding which patients with nonalcoholic fatty liver disease should be surveilled for development of HCC, he added.

“Today, we have no biomarkers. No clue to understand which of these patients—millions worldwide—deserve surveillance or not,” said Piscaglia. “This is a big, hot question because the patients would like to know if they are at risk of developing cancer or not.”

References

1. Piscaglia F. Precision medicine in HCC: what do the guidelines say? In: Proceedings from the 12th International Liver Cancer Association Annual Conference; September 14-16, 2018; London, United Kingdom.
2. Zhu AX, Kang Y-K, Yen C-J, et al. REACH-2: A randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib. J Clin Oncol. 2018;36(suppl; abstr 4003).

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