What Should Patients Know About Treatments for Advanced Liver Cancer?

Lisa Hatfield:

What new and promising treatments are emerging for advanced liver cancer, and how can patients learn whether these are options for them?

Dr. Augusto Villanueva:

So, the management of advanced stage liver cancer has changed dramatically in the last 10 years. And particularly in the last 5 years. And what has changed in the last 5 years has been the introduction of immune-based therapies. So, immune-based therapies now are the backbone of the treatment of patients with liver cancer. 

There are different regimes, different combinations, and they’re very effective in a subset of patients. Between 15 to 30 percent of the patients will have what’s called an objective response when they’re treated with immune-based therapies. And some patients, the response is dramatic. It’s spectacular. Responses that we haven’t seen ever. So, it is true that some patients and, unfortunately, we don’t know who they are, so we don’t know up front who’s gonna benefit significantly from these immune-based therapies. So that has changed.

And certainly, now that we see these remarkable tumor responses, we’re starting to consider more radical treatments for these patients. So, let me give you an example. 10 years ago, if you had an advanced HCC, you would receive treatment with systemic therapies, mostly sorafenib (Nexavar), and you would have prolonged survival. Now, with the new treatments, we can see significant regression of the tumor to a point where surgery or liver transplant can be considered again. And that’s something that is new. Obviously it’s not an option for everybody. It’s an option for some patients, but it can be life-changing.

So, I think that connects to what we talked about, being evaluated in a transplant center. Because now that we can apply systemic therapies more widely with these immune-based therapies that provide significant tumor responses, we start to reconsider more aggressive treatments in these patients.

Lisa Hatfield:

Okay, thank you. And do you have an [ACT]IVATION tip for that question?

Dr. Augusto Villanueva:

I think that my [ACT]IVATION tip would be that there are many treatment options for advanced HCC, most of them are immune-based. And they have changed the natural history of the disease, to a point where we can even consider surgery or transplant if patients achieve significant response with these systemic therapies.

Lisa Hatfield:

Dr. Villanueva, for patients hearing about immunotherapy or targeted therapies for the first time, what should they know about the benefits, side effects, and how these treatments may impact daily life? And I might back up first ask you to give a brief definition of what is immunotherapy, and then talk about the side effects and benefits, please.

Dr. Augusto Villanueva:

So, immunotherapy has transformed the management of cancer in general. Actually, the people who discovered and developed these therapies won the Nobel Prize a number of years ago. So essentially what these treatments do, they activate or reinvigorate the immune system to be able to recognize the tumor cells and eliminate the tumor cells. 

Now, the good thing in liver cancer is that because of the cirrhosis that most patients have, traditional chemotherapy was either not effective or too toxic for patients with liver cancer. So conventional chemotherapy was not being used, was not being applied in liver cancer. Now, with immunotherapy, it’s different. Because the side effects, the safety profile is much more favorable in patients with cirrhosis. So we’re able to treat these patients with immune-based therapies.

So, the treatments are generally well tolerated. The main side effects are related mostly to the hyperactivation of the immune system, to a point that it starts attacking other organs that we don’t want the immune system to attack, so the lungs, the kidneys, sometimes the liver. So these are the main side effects. It’s like this overstimulation of the immune system. But compared to the side effects of conventional or traditional chemotherapy, they’re significantly lower in patients with cirrhosis.

In terms of the targeted therapies, it was the first type of systemic therapies developed for liver cancer. These are what’s called small molecules, pills that are specifically targeted to antagonize the effect of a specific mutation or a signaling pathway that is activated in the cancer cells. So there are less specific and have a different type of side effects. In liver cancer, the ones that are recommended generally can increase the blood pressure, can cause some protein in the urine, or they can cause some skin reactions, so those are the main side effects of targeted therapies in liver cancer.

Lisa Hatfield:

And you mentioned that these are fairly well-tolerated, typically, especially compared to traditional chemotherapy. But as a cancer patient myself, when I hear my doctor say that, I sometimes want to know, well, what does that mean? Does it mean that if I work full-time, I might have to drop down to half-time? And I understand that every patient’s going to respond differently. But what do you tell your patients? How will that impact their life in general, or their daily living, with these immunotherapies and targeted therapies?

Dr. Augusto Villanueva:

So, again, it depends on the patient, but most of them, the impact doesn’t significantly change their routine life. So unless they develop specific, again, pneumonitis, which is an inflammation of the lungs, or nephritis, which is an inflammation of the kidneys, with functional impairment, or fever, all these types of immune-related side effects, most of them can continue with their lives normally. So, that’s the beauty about these treatments in liver cancer, at least.