Dr Feun on the Evolving Treatment Paradigm in HCC

Lynn G. Feun, MD, medical oncologist, professor, Department of Medicine, co-leader, Melanoma Site Disease Group, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the evolution of treatment approaches in hepatoceullar carcinoma (HCC), the influence of immunotherapies on patient outcomes in this armamentarium, and ongoing avenues of investigation within in the field of HCC management.

Historically, treatment options for HCC have been limited, with chemotherapy serving as the primary approach, Feun begins. However, this treatment paradigm began to shift approximately 15 years ago with the development of TKIs such as sorafenib (Nexavar), as well as other targeted approaches including lenvatinib (Lenvima), Feun says, adding that these agents demonstrated superior activity when compared with traditional chemotherapy.

In recent years, the emergence of immunotherapy has improved patient outcomes in HCC, thereby shifting treatment approachesfor this patient population, Feun details. Immunotherapy has demonstrated the ability to induce substantial responses, extend patient survival, and represents a potentially curative option for select patients, he says. Notably, immunotherapy has proven to be more effective than some standard TKIs alone and has increased survival rates when used in combination with these agents, Feun reports.

For example, the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) in the phase 3 IMBrave150 trial (NCT03434379) improved overall survival (OS), progression-free survival, and overall response rates vs the TKI sorafenib. These data led to the regimen's approval in this population in May, 2020. Additionally, the PD-L1 inhibitor durvalumab (Imfinzi) and the anti-CTLA-4 inhibitor tremelimumab (Imjudo) improved OS vs sorafenib in patients with unresectable HCC in the phase 3 HIMALAYA trial (NCT03298451), leading to its approval in October, 2022. 

Looking to the future, novel checkpoint inhibitors such as TIGIT inhibitors have exhibited noteworthy activity in HCC, and clinical trials are continually exploring the potential of anti- TIGITantibodies combined with immunotherapy, Feun states. Additionally, the development of other targeted therapies shows substantial potential for reshaping the landscape of HCC treatment, providing new options for patients with this disease, Feun concludes.