Liver Cancer Experts Mark a Decade of Milestones in HCC

Richard S. Finn, MD

Although it has been nearly 10 years since a new drug was approved for the treatment of patients with hepatocellular carcinoma (HCC), the past decade has been marked by advances on the scientific and radiology fronts and the prospects for the development of new therapies are bright.

That was the assessment of experts in the field who are leading the 10th Annual Conference of the International Liver Cancer Association (ILCA) in Vancouver, Canada. ILCA leaders compared the current state of affairs in the care of patients with liver cancer with the outlook when the organization was formed in 2006 during a press conference to kick off the gathering.

The milestones include a growing recognition that liver cancer is a significant health problem worldwide and needs additional investment of research dollars to improve patient outcomes, said Richard S. Finn, MD, an associate professor of Medicine at the UCLA Geffen School of Medicine and current ILCA president.

“Liver cancer is one of the leading causes of cancer death globally, yet the amount of resources and attention given to it were not on measure with other common malignancies,” said Finn, referring to the initial meeting.

“It also has some very unique characteristics and, that is, it’s not just a cancer. Ninety percent of the patients we manage have underlying liver disease, commonly from viral hepatitis, whether hepatitis B or C or alcohol-related liver disease and, increasingly, there’s an association between liver disease and diabetes and metabolic syndrome,” Finn said.

Peter R. Galle, MD, PhD, a past president of ILCA, said that there has been a long wait for new systemic therapies for patients with HCC, the most common form of liver cancer.

He noted that the organization was formed around the time that sorafenib (Nexavar), a multikinase inhibitor that blocks tumor angiogenesis, was being evaluated. In 2007, the FDA approved sorafenib for the treatment of patients with advanced, unresectable HCC based on a 3-month improvement in median overall survival (OS) compared with placebo (10.7 months vs 7.9 months; HR, 0.69).¹ It remains the only approved targeted drug for HCC.

“At the time the first meeting was planned, there was virtually no systemic therapy available for patients with advanced-stage disease,” said Galle, who is director of the Department of Internal Medicine at Mainz University Medical Centre in Germany. “Because of the development of this new therapy, our conference was stimulated by the idea that this is a treatable disease.”

The ILCA leaders believe that regorafenib (Stivarga) is on the verge of gaining approvals from regulatory agencies in the United States and elsewhere, after demonstrating a 38% reduction in the risk of death compared with best supportive care in patients with unresectable HCC who progressed after receiving sorafenib.²

Regorafenib, which impedes VEGF and multiple other kinases, improved median OS by 2.8 months compared with placebo in the phase III RESORCE trial (10.6 months vs 7.8 months; HR, 0.62). Bayer Pharmaceuticals, which developed sorafenib, has submitted the RESORCE findings to the FDA and the European Medicines Agency for approval.

“We started with nothing,” Galle remarked, adding that there has been “slow progress, but definitely progress.”

Finn acknowledged that the wait for another therapy has been frustrating. “Investigators can get discouraged but what’s very exciting on the horizon is now we have a new drug, which will eventually be approved for this indication,” he said.

He also noted that there are ongoing phase III trials of other novel agents, including a study evaluating lenvatinib (Lenvima) versus sorafenib as frontline therapy for unresectable HCC (NCT01761266) and the REACH-2 trial comparing ramucirumab (Cyramza) with placebo as a second-line therapy following sorafenib (NCT02435433).

Meanwhile, new techniques in radiological interventions have improved care, along with “a revolution in molecular biology and our understanding of the relationship between liver disease and liver cancer,” said Finn.

Jessica Zucman-Rossi, MD, PhD, ILCA executive secretary, said such scientific advances have helped usher in a more personalized approach to treating patients with HCC. “We were considering most patients as a uniform population but now we are thinking about how to have more precise treatment for each patient,” said Zucman-Rossi, a professor of Medicine at the University Paris Descartes in France.

Similarly, evaluating patients with risk factors for progression of HCC has moved from broad considerations into more finely tuned algorithms, representing a major change in the field, said Morris Sherman, MB BCh, PhD, FRCP(C), ILCA treasurer.

“Now there are a number of different ways of assessing patients who are at risk, the objective being to exclude those who don’t need screening because that increases the cost and decreases the efficacy of the screening program,” said Sherman, of the University of Toronto. “We’re trying to hone in patients who are at greatest risk. That also has been one of the bigger changes over the last 10 years.”

References

1. National Cancer Institute. FDA approval for sorafenib tosylate. http://goo.gl/QNQJy6. Updated November 26, 2013. Accessed September 9, 2016.
2. Bruix J, Merle P, Granito A, et al. Efficacy and safety of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: results of the international, randomized phase 3 RESORCE trial. Presented at: 2016 World Congress on GI Cancer; June 28 - July 2, 2016; Barcelona, Spain. Abstracts LBA03.

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Finn said treating patients with liver cancer requires a complex multidisciplinary management team, which is reflected in an ILCA membership that includes hepatologists, oncologists, surgeons, pathologists, and other specialists.