Cabozantinib May Be a Match for Regorafenib in Second line Advanced HCC
May 19, 2020 07:00pm
By Nichole Tucker
In an interview with Targeted Oncology, Michael A. Choti, MD, discussed what he’s looking forward to at the 2019 ISGIO Annual Conference and why this meeting is so important to physicians in the field of GI oncology. He also highlighted the surgical approaches to treating patients with HCC from his own experiences as a surgical oncologist, as well as the challenges associated with these treatment options.
Michael A. Choti, MD, MBA, FACS
As the incidence of cases of hepatocellular carcinoma (HCC) continues to rise, the treatment landscape continues to evolve as well. Patients with early-stage disease have a number of surgical options available, as well as systemic and targeted therapeutic approaches. The treatment landscape for patients with advanced HCC has also advanced with several more options becoming available over the past few years.
If HCC is caught early on, physicians have a few different surgical options, including liver resection and transplant. However, a number of challenges still exist with these treatment options. For instance, to be eligible for surgical resection, the patient must have a healthy, functioning liver so that when part of the liver is taken out, the remaining liver can function and regenerate. For transplant-eligible patients, healthy liver donors are a precious resource, and patients can remain on the wait list for an extended period of time; during the waiting period there is a risk that the cancer may spread.
Another options for patients with early-stage disease is ablation; rather than cutting out a part of the liver, physicians can use a probe to freeze or burn out the cancer if it is in a favorable position, with either microwave or radiofrequency ablation. However, this option is only available for those with very small sites of disease that can be reached by probe.
For patients with larger tumors, intra-arterial options are available, including the use of beads that are embedded with either chemotherapy or radiation, such as yttrium-90 (Y-90). Y-90 and related treatments are able to attack the liver cancer directly, but these are not curative options. However, these treatments can help in shrinking the tumor.
When patients are diagnosed with advanced HCC, surgical approaches are not usually an option. For these patients, systemic and targeted therapies, as well as immunotherapies, become the best treatment. At the 2019 International Society of Gastrointestinal Oncology (ISGIO) Annual Conference, participants can expect to hear more on these options, as well as the data that have come out over the last 12 months on recent advancements.
“It’s going to be an exciting meeting. I think we have all the world’s experts in gastrointestinal [GI] oncology, including the experts in HCC, so I’m looking forward to [hearing from these experts],” said Michael A. Choti, MD, MBA, FACS. “The meeting emphasizes a review of the most updated material by the world’s thought leaders and experts in GI oncology.”
In an interview withTargeted Oncology, Choti, division chief of surgery at Banner MD Anderson Cancer Center, discussed what he’s looking forward to at the 2019 ISGIO Annual Conference and why this meeting is so important to physicians in the field of GI oncology. He also highlighted the surgical approaches to treating patients with HCC from his own experiences as a surgical oncologist, as well as the challenges associated with these treatment options.
TARGETED ONCOLOGY:Can you discuss how you have seen the treatment landscape of HCC evolve over the last few years?
Choti:Liver cancers, the incidence seems to be going up. We can make some comments about how we’re making advances in hepatitis B and hepatitis C vaccines, pronounced reduction in cirrhosis-associated HCC but because of increasing obesity, we’re seeing increasing incidence of what’s called NASH-associated liver disease. That is an increasing cancer. Even in the United States, we’re still seeing that HCC continues to be a problem.
From the surgical standpoint, [the treatment landscape] has been relatively stable. The advances have been mostly, in the last couple years, related to systemic therapies and immunotherapy that’s available for liver cancer.
I chaired the hepatobiliary TASK force for Cancer Therapy Evaluation Program (CTEP) and NCI about 5 to 10 years ago, and there was such a paucity of clinical trial options for patients with HCC and now, it’s booming. There’s a lot of ongoing trials and ongoing new therapies. I’m a surgeon, but from a systemic standpoint, there are increasing options. The landscape has changed significantly in the last couple of years.
TARGETED ONCOLOGY:What are the treatment options for patients with HCC, and what challenges need to be addressed in this space?
Choti:The best treatment, if eligible, is liver resection, just cutting out the cancer. If it’s caught early and is eligible and resectable, then surgical removal of the liver to remove the HCC for localized cancer is really the best treatment and the best option for cure. The challenges are that diagnosing it and finding it while it is still localized and eligible for surgery is still a challenge. To detect, to screen, and to find these early so that they can be caught early and removed.
The other challenge is, as I mentioned, these are often associated with underlying liver disease. For us to remove part of the liver for the liver cancer, the remaining liver has to be healthy to function, so our patients already have underlying cirrhosis and underling damage of their liver from their disease that caused the cancer, then most patients are at higher risk. It’s like a patient with lung cancer who has terrible lungs; you can’t remove even a little part of the lung because they don’t have enough lung function to survive. It’s the same with the liver. In someone with a healthy liver, I can remove three-quarters of someone’s liver, and the remaining liver will be healthy; they will do well postoperatively, and the remaining liver will regenerate. However, when someone has a damaged liver, which is commonly associated with HCC and cirrhosis, you can’t be cutting out large parts of the liver. There’s just not enough liver to function. That’s 1 problem.
The other option with surgery in patients with early liver cancer is transplant. If someone has a very damaged liver and can’t handle cutting up part of the liver, but the cancer is caught relatively early in someone with a lot of cirrhosis, another alternative is to take out the whole liver and put in someone else’s liver, for a liver transplant. That is also associated with a lot of challenges. For 1, there’s a limited number of donor livers so we have a precious resource. Also, patients are on the waiting list for a very long time for a donor liver, but it’s hard to wait a long time with cancer since it can spread in the meantime. The third problem with transplant is that you’re suppressing the immune system, so not all patients with liver cancer are eligible for transplant. You need to have very early-stage liver cancer under some defined criteria for patients who are eligible for transplant. It’s very limited, but even those patients have to be waiting on the transplant list for a long time.
Those are the challenges, catching it early [enough to get] potentially curative therapy with either resection or transplant. There are other options in those patients who have caught it early. For example, we can do a procedure called ablation, where instead of cutting it out, you can put a probe in there and burn it or freeze it, using microwave ablation or radiofrequency ablation to burn the spot. Those are, again, only for selected folks with very small liver cancers, in favorable locations within the liver. The advantage to this is you don’t have to operate, and you don’t have to cut out sometimes a large part of the liver. Those are all the options for patients with early cancer eligible for transplant, resection, or ablation. Unfortunately, still the majority of patients are not eligible for those types of potentially curative therapies.
There’s another class of therapies that are also widely used, and that’s intra-arterial where beads or seeds are put in through the artery and directed right to the tumor. Those you can do for larger tumors and those beads can be either embedded with chemotherapy or are radioactive beads called Y-90 that can also be used for liver cancer to attack the tumor directly. It’s not a guarantee that those are wiped out, but those are patients with liver-only cancer. Their disease is localized to the liver, but it is too large or in a bad location that is not [eligible for surgery], so we can then use these liver-directed radioactive beads or chemotherapy beads. It doesn’t have as high a success or cure rate, but it can definitely shrink the cancer.
Those are the treatment options. The other challenge with that is a large number of patients with liver cancer are treated with those intra-arterial approaches.
There’s another approach occasionally used as well, which is radiation beam therapy. These are not radioactive beads but external radiation treatments, called stereotactic body radiotherapy. That’s in a select number of patients, locally treating. That’s what in our armamentarium for local regional options. There are obviously some challenges there.
TARGETED ONCOLOGY:What are the treatment options for patients with advanced disease?
Choti:The biggest advancements have been, not in curing patients, but I would say the biggest change is now we have more options for patients with advanced disease with disease either throughout the liver or when it has spread beyond the liver, with the systemic therapiesimmunotherapy and targeted therapies. Again, the problem with those patients is that HCC is associated with underlying liver disease. If somebody has bad underlying liver disease, bad cirrhosis, there aren’t many options. You can’t do surgery on them. Maybe you can do transplant if the cancer is caught early, but those patients with advanced disease have [other options].
Liver disease can be categorized by mild cirrhosis called Child-Pugh A, to moderate cirrhosis, which is Child-Pugh B, and more severe cirrhosis is called Child-Pugh C. Anybody with a B or C cancer has fewer options, including the systemic or immune therapies for people with B and C. One of the big challenges is again the association of HCC with underlying cirrhosis in not all but some patients. Child-Pugh A patients with mild or no cirrhosis are more able to not only do surgery, ablation, or intraarterial therapy, but those patients are more likely to be eligible, even if the cancer has already spread but the cirrhosis is mild. We can offer them the systemic or targeted therapies or immunotherapy as well.
TARGETED ONCOLOGY:What advances or innovations have you seen over the last year in HCC that attendees should look forward to seeing at this meeting?
Choti:The real advances over the last 12 months are related to the systemic therapies. That’s something I’m not an expert in, as a surgeon, but those are where the advances have occurred. As I mentioned, these are primarily related to targeted therapies. There’s already sorafenib (Nexavar) and regorafenib (Stivarga), but now there are studies for other targeted therapies, like tyrosine kinase inhibitors, and other drugs that are emerging. Immunotherapies, like nivolumab (Opdivo) and others, are also big.
The advances over the last 12 months are associated with emerging evidence of more effective systemic therapies. However, the challenge in that respect is that 5 years ago we had no systemic treatment at all, or all we had was maybe sorafenib and even sorafenib had a pretty limited benefit and had adverse effects or issues. We had a very limited armamentarium for systemic therapies 5 years ago or so, but now the advances over the last year or 2 have made more choices for systemic therapies. The challenge is now it’s not necessarily as clear what to offer first-line and second-line. There are a lot of ongoing trials now in what’s the best way to sequence the therapies, both targeted therapies or systemic therapies, what order and whether we should start with sorafenib or start with different agents and so forth.
The other challenge is with these other local regional therapies like chemoembolization or radioembolization. How do we integrate these in with the systemic therapies? So, in a patient with liver cancer that spreads, we may as well give the systemic therapy, immunotherapy, or targeted therapy combined with intra-arterial therapy, or do we start with systemic or a local therapy? Not only are there challenges now having more options available for these patients with advanced disease, but what is the sequence in which we should offer therapies and which of the choices of the targeted therapies or immunotherapies should we offer? That’s where we are now.
We’ve gone from where we had nothing systemically to offer patients, and we were just ringing our hands over that. Now we are in a position where we have options, more options, on the systemic side, but the challenges are which of these therapies has this evidence in trial results. What’s the best order in which we use the systemic therapies? How do we incorporate the systemic therapies with the regional or local therapies? Finally, the other challenge is we know a lot of these patients have underlying liver disease cirrhosis that confounds the ability to use a lot of these treatments. We still have a lot of challenges ahead.
TARGETED ONCOLOGY:As ISGIO is heading into its 16th year, what are you most looking forward to at this year’s meeting?
Choti:It’s going to be an exciting meeting. I think we have all the world’s experts in GI oncology, including the experts in HCC [at this meeting], so I’m looking forward to [hearing from these experts].
The meeting emphasizes a review of the most updated material by the world’s thought leaders and experts in GI oncology. Also, it’s in a format that is particularly appealing. There are cutting-edge review lectures. There are some talks that are in the debate format looking at option A or option B, drug X versus drug Y. I’m debating on the management of pancreatic cancer, for example. There’s also a lot of case-based discussions. For example, I’m monitoring a case that’s being presented specifically related to HCC on whether to do transplant or resection. That is very appealing to an audience rather than just hearing data out of context or just hearing hypotheticals. The audience and oncologists can then relate to how these experts make decisions about how to manage patients with specific cases.
The final thing is the participants have the option to interact with these key opinion leaders during the meeting. They can discuss cases and get the chance to meet with these thought leaders. I think it’s a particularly exciting meeting and a terrific opportunity.
It also reviews the field from soup to nuts. It’s not just an HCC meeting or just a pancreatic cancer meeting, which is too specific but it’s not just a general meeting like ASCO that covers all cancers. It focuses just on GI oncology from soup to nuts, from esophagus to stomach to rectal to liver to pancreas to neuroendocrine cancers. It covers the whole spectrum of GI oncology, which is also very appealing. You can get a primer of the most updated in GI cancer management in 2 days.
I think the last nice feature is it is particularly multispecialty. A lot of these meetings are all for the medical oncologists, it’s all about chemotherapy alone, for example. But I would make the case that even if someone in the audience is just a medical oncologist or just a surgical oncologist, for that individual, they will learn the multidisciplinary management. Medical oncologists will hear from surgeons, radiation oncologists, or interventional radiologists, which is particularly appealing. It’s truly multidisciplinary. Even if your specialty is chemotherapy or surgery, you can learn more from your colleagues in other specialties. So, I think that it’s going to be a very exciting meeting this year.
To learn more or register for ISGIO, please visithttp://www.isgio.org/.