Morris Sherman, MD
The past 18 months have included 3 drug approvals in the United States for the treatment of patients with hepatocellular carcinoma (HCC), with additional targeted therapies and checkpoint inhibitors in late stages of development. Moreover, the oncology community are awaiting later-phase data that will undoubtedly impact treatment decisions, explained Morris Sherman, MD, PhD.
The emergence of these therapeutic developments, and the excitement surrounding them, were discussed during the 12th Annual Conference of the International Liver Cancer Association (ILCA), held in London, United Kingdom.
In an interview with OncLive
, Sherman, professor of Medicine at University of Toronto and president of ILCA, shared his insight on the news and discussions coming out of this year's meeting, the surge of immunotherapy and targeted therapy research, optimal sequencing approaches, and the challenges that remain in treating patients with HCC.
OncLive: How would you characterize the overall state of the HCC landscape today?
: Immunotherapy looks very promising, but we still are waiting for the phase III results to confirm that, for example, nivolumab (Opdivo) is an effective treatment [in CheckMate-459]. At the moment, it certainly looks that way, but we need the final data. There are several other immunotherapies, and if nivolumab really turns out to be good, then presumably some of these other immunotherapies will also be very [effective].
We are going to find that, even if nivolumab works very well, there are still going to be a large number of patients who don’t respond—and that’s going to be one problem.
The second problem is that, with whatever treatment is going to be effective, there is going to be a big issue of access. This is because these are all going to be [very] expensive, [various parties] will struggle to find the resources to pay for this. Given that liver cancer is the second most common cause of cancer death, and the countries that have the most liver cancer are often poorer, access is going to be a major issue.
Let’s discuss the available frontline targeted therapies. Are there factors that would help you choose between lenvatinib (Lenvima) or sorafenib (Nexavar) for patients with HCC?
The factors that would lead someone to choose one drug over another are the same no matter what 2 drugs you’re comparing: how effective they are and how much toxicity they cause. There is not really a great deal of difference in either the efficacy or toxicity in those drugs, so it is going to be very much a question of individual choice.
I’m not sufficiently convinced by the current data that there are any patient factors suggesting you should use one drug or the other. I know that there are data out there suggesting that, for example, that lenvatinib is associated with hypertension—that is not a deciding factor for me. The differences are still relatively minor.
What are the considerations for sequencing therapies for patients with advanced HCC?
At the moment, the only solid sequencing data that we have is the sorafenib–regorafenib (Stivarga) sequence or the sorafenib–cabozantinib (Cabometyx) or sorafenib–ramucirumab (Cyramza). The sorafenib–nivolumab data are a little less convincing, simply because the study was a phase II study, and not a phase III study. For lenvatinib, we don’t really have any data on sequencing therapy at all. The same kinds of considerations will apply post-lenvatinib as you have post-sorafenib, but that still needs to be demonstrated.
What are the most pressing challenges today in treating HCC?
Early diagnosis, or the lack of early diagnosis [is a big challenge]. The majority of patients, even in well-developed countries, present with incurable disease. Yet, theoretically at any rate, all liver cancer is curable at some point. The question is to find those patients when the cancer is treatable—the cure rate is going to go up substantially if we’re able to find those patients.
Are there clinical trials that you’re watching closely?
There are a number of studies out there that are going to report out in the near future. There is the phase III nivolumab study [CheckMate-459]. There is the pembrolizumab study…there are a couple of studies about bevacizumab and atezolizumab, and there was lenvatinib and pembrolizumab. Those are the big studies that are out there. The one that we are most interested in at this point is the phase III nivolumab data. If that’s good, then that’s going to be the first-line drug.
Since this is an international conference, can you discuss some of the areas in which different regions can learn from one another or share ideas?
One of the biggest differences is that treatment in the East is more aggressive than it is in the West. Some data would suggest that more aggressive treatment is associated with better outcomes. However, what is not made clear is whether this more aggressive treatment is also associated with more toxicity. It’s very difficult to assess the toxicities involved in some of these treatments in Asia, for example. I’m not yet ready to advocate for more aggressive treatment in the West.
We also have data from the West that suggest that if you don’t stick to the recommended treatment, results are worse. Those studies obviously do include toxicity, so I’m not sure yet that we should be going the more aggressive route.
The other thing is, in some centers in the East, they cling to the use of chemotherapeutic agents. We know that chemotherapy doesn’t work, and we know it’s toxic, but they continue to use it.
I’m a little disconcerted by the number of different staging systems that are being postulated both in the East and in the West, and somehow the staging systems that are described in the East don’t match the staging systems that are described in the West. There is something there that is not gelling properly.
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