Analyzing the Immunotherapy Landscape for Advanced HCC

Namrata Vijayvergia, MD, Gastrointestinal Medical Oncology, Fox Chase Cancer Center, and Christopher Lieu, MD, Gastrointestinal Medical Oncology, University of Colorado, detail how immunotherapy has changed the landscape for the treatment of metastatic hepatocellular carcinoma (mHCC) in recent years, as well as the considerations they have for administering immunotherapy to their patients.

Dr. Lieu: It’s remarkable to think that in 2008, there were no FDA-approved therapies for mHCC. Then suddenly, sorafenib emerged. For many years, we relied on sorafenib, but now there has been a virtual explosion of drugs to treat mHCC, with a major advancement being the implementation of immunotherapy. I would like to hear your perspective on how immunotherapy has changed the treatment landscape for mHCC and how you approach incorporating immunotherapy for HCC.

Dr. Vijayvergia: Indeed, I remember the days when sorafenib was the only option we had, and treating patients was quite challenging. Working in an area where HCC is highly prevalent, having various treatment options now is a game-changer. Initially, we had single-agent PD-1 inhibitors like nivolumab, which showed promise, especially for patients with B7 or Child-Pugh instability. However, in 2021, the second-line indication for nivolumab was withdrawn. The atezolizumab plus bevacizumab (atezo/bev) combination marked a significant shift with the IMbrave study. As a medical oncologist, I started seeing patients at earlier stages, including those with locally advanced or rapidly progressing disease. Atezo/bev has become my go-to treatment due to its impressive long-term overall survival of more than 19-20 months.

The recent addition to our options is the durvalumab plus tremelimumab (durva/treme) regimen, which I have not used as extensively as atezo/bev due to its novelty. However, it has proven to be a very effective option, administered every 4 weeks, with an average survival of 16-17 months. The introduction of these treatments has indeed revolutionized the approach to hepatocellular carcinoma.

Dr. Lieu: Absolutely, the combination of atezolizumab and bevacizumab has significantly changed the treatment landscape, especially in the frontline setting. Choosing between atezo/bev and durva/treme can be challenging. How do you decide which regimen to recommend, and is there a specific population for whom you prefer one over the other?

Dr. Vijayvergia: When considering atezo/bev versus durva/treme, the trial populations were quite similar, except for contraindications to bevacizumab in the atezo/bev study. To differentiate, I focus on bevacizumab eligibility. If a patient has advanced cirrhosis with evidence of varices or a history of varices, I tend to avoid bevacizumab due to potential complications. My initial inclination is towards atezo/bev, simply because it has been available for a longer time. However, if there is any contraindication to bevacizumab, I lean towards durva/treme. Additionally, some patients prefer the 4-week treatment schedule of durva/treme over the 3-week schedule of atezo/bev, especially if they travel from afar. These considerations guide my decision-making between the regimens.

I have a question for you, though. If we start with durva/treme in the frontline setting, the patient has not been exposed to a tyrosine kinase inhibitor (TKI) for the second line. On the other hand, starting with atezo/bev involves both VEGF-targeted therapies and immunotherapy in the frontline. How do you approach this potential sequencing dilemma?

Dr. Lieu: That is an interesting point. The classes of drugs available include immunotherapy and VEGF-targeted therapies. When choosing durva/treme in the frontline, it simplifies the second-line decision, as the patient has not experienced a TKI yet. However, if we start with atezo/bev, the sequencing for the second line becomes less straightforward. I often consider factors like bevacizumab contraindications and patient preferences for treatment schedules when making these decisions. It is a challenging aspect that would benefit from more research and investigation. The ideal sequencing strategy remains a topic that requires further exploration, especially given the evolving landscape of treatments for HCC.

View their continued conversations, including Biomarkers of Response and Sequencing for Immunotherapy in Advanced HCC and Toxicities and Duration of Treatment for Immunotherapy in Advanced HCC.