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 unmet needs that remain to be addressed in hepatocellular carcinoma (HCC), including challenges regarding the navigation and sequencing of treatment options.

The expansion of available first- and second-line systemic therapeutics in the HCC armamentarium have greatly improved patient prognosis However, understanding the optimal selection and sequencing of these options presents aunique challenge for clinicians, Noonan begins.

Many of the large, phase 3 trials in HCC treatment are unlikely to be repeated in a setting that includes sequencing evaluations, Noonan says. Additionally, patient characteristics that present in the community setting often do not align with original eligibility criteria for patients being evaluated on clinical trials, Noonan explains. For example, studies supporting the FDA approval of current systemic therapies only included patients with Child-Pugh A disease in their eligibility criteria. As a result, there are a limited number of treatment recommendations for patients with HCC who are classified as having Child-Pugh class B or C cirrhosis, Noonan says. Therefore, identifying viable therapeutics for this population is a significant unmet need, she emphasizes.

Many patients with HCC who have cirrhosis of the liver will also experience comorbid organ dysfunction, Noonan continues. This can include liver dysfunction and hepatorenal syndrome. Hepatorenal syndrome predominantly occurs in patients who have ascites originating from portal hypertension, and thrombocytopenia due to splenomegaly, Noonan details. Advanced chronic liver disease is associated with poorer prognosis, and patients with this condition often have difficulty finding safe and effective therapies, Noonan adds. This presents another unmet need that remains to be addressed through future research, Noonan concludes.

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Anne M. Noonan, MBBCh, discusses unmet needs that remain to be addressed in hepatocellular carcinoma, including challenges regarding the navigation and sequencing of treatment options

Dr Noonan on Challenges Regarding the Sequencing and Selection of Therapies 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; 

the FDA approval of durvalumab plus tremelimumab for the treatment of adult patients with unresectable HCC

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.

Anne M. Noonan, MBBCh, discusses recent practice-changing trials for the treatment of patients with hepatocellular carcinoma.


Anne M. Noonan, MBBCh

Articles

Dr Noonan on Challenges Regarding the Sequencing and Selection of Therapies in HCC

Dr Noonan on Practice-Changing Trials in HCC