Physician’s Weekly recently spoke with Robert Gish, MD, FAASLD, a self-identified hepatologist and published author of papers focused on hepatocellular carcinoma (HCC), about the use of atezolizumab plus bevacizumab (AV therapy) as a first-line treatment for patients with advanced HCC and what the latest IMbrave-150 study results mean to him and his patients.
PW: What does it mean for patients with advanced HCC to now have another medication option, after so many years with limited options?
RG: Up through 2015, we had one drug. Then we had a second drug, fegorafenib, and then a series of drugs came out: cabozantinib, ramucirumab, and then lenvatinib. These drugs offered just slight incremental improvements in terms of survival, moving from 6 to maybe 13 months median overall survival between 2005 and 2020. Then, suddenly, he had AV therapy, which moved median survival to 20 months. That’s not quite a doubling, but it’s a huge increase. That’s Earth-shaking—an almost doubled median overall survival with less side effects, which is a wonderful trade-off.
Did the availability of another option for this patient population open the door for more options that are in the pipeline?
Recently, DT therapy (durvalumab plus tremelimumab) was approved. That has similar overall survival that is slightly less numerically than AB therapy, but very, very high. I’d call DT therapy a co-first-line therapy. I wouldn’t necessarily use it first, first line, but there are certain patients—such as those with varices—for whom I would use DT therapy. And there are at least 10 other drugs in development, and I think at least five will be approved in the next 3-5 years. So, very soon, we’ll have a combination of checkpoint inhibitors and other targeted therapies that will be extensive. We’ll have 3, 4, or 5 choices of different combinations. I would suggest this next wave will have a median overall survival of up to about 25 months.
Results of the IMbrave-150 study update in 2021 helped establish AB therapy as a first-line option for patients with advanced HCC. How did the study results differ from those of Himalaya?
Therapy has about a 20-month median survival. DT therapy has about a 17-month median survival, so numerically slightly less. There appears to be an interesting tale that people who do respond to DT therapy can have a very long, durable response; it also doesn’t enhance bleeding risk like you have with bevacizumab; VEGF inhibitors have an ability to change how the blood vessels clot. It is super important to think about these contrasts when one medicine might be used over another.
IMbrave-150 participants all had mild liver disease. We don’t have really good drugs for patients with more advanced liver disease, so it’s super important to keep that in mind. Response was good across all groups, except maybe those with fatty liver-induced cirrhosis and fatty live-induced liver cancer. We are looking for drugs that would work better in that setting.
What else should your colleagues know about treating patients with advanced HCC?
Those who use AB or DT therapy need to know how to manage autoimmune events; that’s critical. I encourage all oncologists to work with a hepatologist with expertise in managing end-stage liver disease; that’s super important.
