Advances in Systemic Therapy for HCC

At the 2023 Symposium on Clinical Interventional Oncology (CIO), Fernando De Zarraga, MD, Baptist Health, Miami, Florida, presented an in-depth discussion highlighting significant advancements in systemic therapy for hepatocellular carcinoma (HCC) from a medical oncology and interventional oncology perspective. 

During the presentation, Dr De Zarraga initiated the discussion by shedding light on the current treatment landscape for HCC, highlighting the prevalent use of oral tyrosine kinase inhibitors (TKIs), with sorafenib and lenvatinib being the primary options. He then introduced the most recent additions to the frontline treatments approved for unresectable HCC: atezoliumab plus bevacizumab and durvalumab with tremelimumab.

A pivotal topic in the presentation was the IMbrave150 study, which led to the approval of atezolizumab plus bevacizumab as a first-line treatment for patients with locally advanced or metastatic HCC and no prior systemic therapy. Dr De Zarraga emphasized the remarkable improvement in overall survival and progression-free survival compared to the standard sorafenib treatment, which marks a significant milestone in HCC management.

Further discussing the treatment landscape, the presentation delved into the HIMALAYA trial. This trial introduced the STRIDE regimen and durvalumab monotherapy as the newest options for frontline treatment, showcasing impressive results in terms of overall survival. Notably, the 48-month survival rates observed were unprecedented in HCC. Additionally, the data indicated that durvalumab monotherapy was non-inferior to sorafenib.

Dr De Zarraga addressed the challenges of sequencing in second-line treatment, particularly for patients who had received sorafenib as their first-line therapy. Several therapeutic options, such as regorafenib, cabozantinib, and ramucirumab, displayed level 1 evidence of survival benefits in the second line, with cabozantinib and regorafenib often being the favored choices.

Child PUA, a challenging subgroup within the Child-Pugh classification, was highlighted as an ongoing challenge across all lines of therapy. The presentation stressed the importance of optimizing sequencing and introducing systemic therapies earlier in the course of the disease. Neoadjuvant strategies and various ongoing trials were discussed as promising avenues for the future.

Another critical point addressed in the presentation was the feasibility of using immunotherapy in the second line after patients had already received immunotherapy in the first line. The data suggested that patients who experienced immune-related adverse events were more likely to respond positively to immunotherapy in the second line.

The presentation also touched upon the ongoing trials exploring the use of immunotherapy post-atezolizumab-bevacizumab treatment, aiming to expand the understanding of immunotherapy's role in the second line and potentially offer improved outcomes for HCC patients.

Lastly, the discussion introduced ongoing trials focusing on the application of adjuvant immunotherapy after curative intent treatments, including liver resection and ablation. It also mentioned a trial exploring the possibility of using immunotherapy in a neoadjuvant setting before liver transplant.

These trials have the potential to redefine treatment strategies for HCC patients, offering new possibilities for improving patient outcomes and overall survival.