Biomarkers of Response and Sequencing for Immunotherapy in Advanced HCC

Namrata Vijayvergia, MD, Gastrointestinal Medical Oncology, Fox Chase Cancer Center, and Christopher Lieu, MD, Gastrointestinal Medical Oncology, University of Colorado, continue their discussion with attention to biomarkers of response (or lack thereof) for immunotherapy in metastatic hepatocellular carcinoma (HCC), as well as immunotherapy sequencing considerations for newly diagnosed patients.

Dr. Lieu: One aspect often discussed with immunotherapy is the search for biomarkers indicating response. In colorectal cancer, MSI-high is a key biomarker, while other cancers like lung and gastric rely on CPS scores, leading to debates. What are your thoughts on biomarkers and immunotherapy in the HCC space, considering it differs from other diseases?

Dr. Vijayvergia: This is becoming increasingly crucial. The MORPHEUS study data shows the emergence of more immunotherapy drugs like the TIGIT antibody, offering potential future options for HCC treatment. However, finding a reliable target remains a challenge. Unlike diseases where PD-L1 scoring, CPS, or TPS are used, these metrics hold no significance, either prognostic or predictive, for HCC immunotherapy. Even distinctions based on viral or non-viral etiology haven not proven reliable. The search for a meaningful biomarker is ongoing, but as of now, there is not any we can rely on.

Dr. Lieu: I concur. It still seems like a 1-size-fits-all strategy, which is not ideal in cancer medicine. Despite that, it simplifies drug prescriptions, given the lack of a definitive biomarker predicting response. However, with the field evolving rapidly, we hope for the emergence of a reliable biomarker. But for now, options are limited.

Speaking of which, considering your previous question, how do you approach sequencing therapy for newly diagnosed HCC patients, and how do you plan backup options for second- and third-line settings?

Dr. Vijayvergia: It is encouraging that we now consider sequencing therapy for advanced HCC, marking a significant improvement from years past. While most patients receive immunotherapy combinations as the frontline option, those with challenging conditions, like Child-Pugh B7 or high, may require alternative strategies. In such cases, using a TKI initially or nivolumab as a single agent is a common approach. For the majority, immunotherapy doublet or IO plus VEGF becomes the frontline choice. After progression, we shift to a TKI, with lenvatinib or cabozantinib being the top contenders. Personally, I lean towards lenvatinib for its better tolerance, especially in patients with cirrhosis. Cabozantinib is an option, and regorafenib remains on the table for later stages.

Dr. Lieu: It is fascinating how we have progressed to considering immunotherapies as frontline options and using tyrosine kinase inhibitors later in the course. As we mentioned earlier, ramucirumab is a proven second-line option, especially for patients with elevated AFPs. However, if they have had prior bevacizumab, it is typically not my first choice.

View their other related conversations, including Analyzing the Immunotherapy Landscape for Advanced HCC and Toxicities and Duration of Treatment for Immunotherapy in Advanced HCC.