Dr Noonan on Practice-Changing Trials in HCC

Anne M. Noonan, MBBCh, assistant professor, the Department of Internal Medicine, chief, Gastrointestinal Medical Oncology Section, The Ohio State University, member, the Translational Therapeutics Program, The Ohio State University Comprehensive Cancer Center–James, discusses recent practice-changing trials for the treatment of patients with hepatocellular carcinoma (HCC).

In recent years, the field of HCC has progressed with the addition of new, effective combination therapies with different mechanisms of action compared with the previous standard of care, Noonan begins. Sorafenib (Nexavar) previously stood as the standard of care for many years; however, 2 landmark studies in the first-line setting that have shown superiority of immunotherapy-based combinations vs sorafenib alone, Noonan explains. 

The phase 3 IMbrave150 study (NCT03434379) examined the combination of bevacizumab (Avastin) and atezolizumab (Tecentriq), and findings showed that the combination produced a significant overall survival benefit of 19.2 months compared with 13.4 sorafenib alone (HR, 0.66; 95% CI, 0.52-0.85). In May 2020, the FDA approved the combination of atezolizumab plus bevacizumab for use in patients with unresectable or metastatic HCC who have not previously received systemic treatment, based on data from IMbrave150.

Another practice-changing study was the phase 3 HIMALAYA trial (NCT03298451) of tremelimumab (Imjudo) combined with durvalumab (Imfinzi) vs sorafenib alone in patients with unresectable HCC. This combination also deliver a superior OS benefit of 16.43 months vs 13.77 months for sorafenib (HR, 0.78; 96.02% CI, 0.65-0.93; P = .0035). These findings supported the FDA approval of durvalumab plus tremelimumab for the treatment of adult patients with unresectable HCC in October 2022.

Durvalumab/tremelimumab also provided clinicians with another option for patients who may potentially not be candidates for anti-VEGF therapies due to risk for bleeding, Noonan concludes.