Researchers Have "New Attitude" About Liver Cancer, Expert Says

Lewis R. Roberts, MB, ChB, PhD

While the liver cancer landscape is not as explosive with novel agents as some other solid tumor types, systemic and surgical advancements are still having an impact on the lives of patients.

In January 2017, a supplemental biologics license application for the multikinase inhibitor regorafenib (Stivarga) was granted priority review by the FDA as a second-line treatment for patients with unresectable hepatocellular carcinoma (HCC).

The application is based on findings from the phase III RESORCE trial, which showed that the median overall survival was 10.6 months with regorafenib plus best supportive care versus 7.8 months for placebo plus best supportive care. This translated into a 38% reduction in the risk of death (HR, 0.62; 95% CI, 0.50-0.78; P <.001).

OncLive: What did you discuss during this State of the Science Summit?

“The main thing is that this is really a time of hope for patients with liver cancer,” says Lewis R. Roberts, MB, ChB, PhD. “For a long time, there was a sense of futility about liver cancer. Many patients presented with very advanced disease; there was not a whole lot that could be done for them. Many patients were only candidates for palliative care. I think that is changing.” During the 2017 OncLive^® State of the Science Summit on Gastrointestinal Malignancies, Roberts, a professor of Medicine at Mayo Clinic, spoke on the current state of HCC. In an interview, he discussed the recent advancements and emphasized the importance of a multidisciplinary approach.Roberts: I tried to remind people that, of all of the major cancers, liver cancer is the most deadly. People are most likely to die within 1 year of diagnosis for liver cancer than for most of the other major cancers.

The other important thing is that, in the United States, we are finding that liver cancer is increasing in its incidence, whereas for many other cancers, we’re actually seeing a decrease in numbers and deaths. We are actually seeing a rise in liver cancer cases; it is becoming a more important cancer here in the United States.

In terms of treatment of patients with liver cancer, the main point of my presentation was the emphasis of multidisciplinary care as we approach patients with liver cancer. Particularly now, we are finding that if we can enroll people who are at risk in the screening program of surveillance for cancer, we can often detect the cancers at an earlier stage.

That gives us more treatment options, like liver transplantation, surgical resection, and different kinds of ablative methods to destroy tumors in the liver. The methods we had before were not appropriate for liver cancer but then [there were] changes in technology and the ability to focus radiation therapy beams on the tumor. It has really shown us that, as long as we are not treating the entire liver, we can safely treat individual tumors and have very good results. Treatments such as stereotactic body radiation therapy, and also proton beam therapy, are really emerging as important treatments for some patients with liver cancer.

You mentioned an increase in liver cancer incidence. What are some of the lesser-known risk factors of this disease?

Having that sense of it’s now a disease that’s treated not such individual specialties, but really by multidisciplinary groups, is the big message.For a long time, the major thing that has driven the rise in liver cancer in this country is the hepatitis C virus. Up until 1990, we didn’t have any way of diagnosing hepatitis C so it became quite prevalent. Then, after people had the infection for 20 or 30 years, they would get cirrhosis or scarring of the liver, then that would lead to development of cancer in the liver. We typically think of people who are born between 1945 and 1965—those are the “boomers” generation—as being the generation that is hardest hit.

After 1990, we had tests for hepatitis C so, since then, we have been able to reduce its transmission in the population. We actually began to address hepatitis C and now, over the last 2 or 3 years, we have had very effective treatments for hepatitis C.

What are some of the biggest remaining challenges in liver cancer?

Now, all we have been seeing has been really been an epidemic of nonalcoholic fatty liver disease. This is the idea that the whole population of this country has been increasing in size, and that’s been a major demographic shift in the last 30 years or so. As people gain weight, they can also deposit fat in the liver that can cause inflammation, can cause scarring in the liver, and can lead to development of liver cancer. We are finding that we are seeing a substantial number of people who are developing liver cancer because of having had fatty liver disease.One big challenge is identifying those people who are at risk for liver cancer and putting them in a surveillance program so we can detect their cancer early. If we can do that, we can deploy the best treatments possible. Then, for the majority of patients right now who are diagnosed with intermediate- or advanced-stage liver cancer, the main challenge is finding good treatments for them.

We currently have only 1 drug—sorafenib (Nexavar)—that is approved for treatment of intermediate- and advanced-stage liver caner. We actually are on the threshold of just having a second drug have a successful phase III trial, the results of which were released last year. We anticipate this other medication, regorafenib, will also become available in the near future for people who have progression of their disease after they have been treated with sorafenib.

Do you anticipate immunotherapy being used as monotherapy or in combinations?

What is the importance of having a multidisciplinary approach in liver cancer?

The other thing that is quite exciting for patents with intermediate- or advanced-stage disease is really the advance in the knowledge of immunotherapies. We are finding that, with early-stage trials in liver cancer, that the immune checkpoint inhibitors and other drugs that boost the immune system or inhibit the way that cancers hide away from the immune system look like they’re also going to be effective in liver cancer. I’m actually very excited about the possibility of being able to add these treatments into the options available for these patients with liver cancer.Our anticipation is that it’s most likely that this will be used in combination with other therapies, as well. There is a lot of research going on to try and understand how these different drug classes can be combined most effectively for the best management of patients.The point I made is that liver cancer is a little bit like real estate. The real estate people says it’s “location, location, location.” It’s very different treating someone who has a liver cancer that’s hanging down at the very tip of the liver. Another patient may have the same size tumor but, if it’s buried right in the center of the liver where all of the other major blood vessels and biliary tubes, etc are, then it becomes a much more difficult thing to approach surgically.

What are the main ideas you hope community oncologists will take away from your presentation?

The location is key, as well as having the recognition that different treatments are better depending on the specific location or the number of tumors that a patient has. It reemphasizes the need to pull all of the different disciplines together so that we can tailor the treatment for a particular treatment according to their specific needs.We are learning to be aggressive with patients, and we are learning that we can combine different treatments—we can use local treatments with systemic treatments and location. That is really a message: to have a hopeful attitude for these patients and also be willing to apply these different treatment options to individual patients to try and give them long-term outcomes.

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. In: Proceedings from the 2016 World Congress on GI Cancer; June 28 - July 2, 2016; Barcelona, Spain. Abstract LBA03.