Newer Therapies at Last Offer Systemic Options for Metastatic HCC

December 12, 2019 by Nicole Ross CRNP, MSN, AOCNP®

Already the third leading cause of cancer deaths worldwide (, hepatocellular carcinoma (HCC) is a continually growing burden as the incidence of obesity, type II diabetes, and hypertension also increase, which may lead to cirrhosis and nonalcoholic fatty liver disease. Its incidence is highest in Asia and Africa, where the prevalence of hepatitis B and hepatitis C may result in chronic liver disease and subsequently HCC. 

Nonsystemic Treatment Options for HCC

Options for treating early-stage disease include liver-directed therapies and surgical resections, both of which are highly dependent on patients’ hepatic function and functional status. Advanced practice providers should individualize treatment plans based on each patient’s needs. Liver resection is the surgery of choice for patients with tumors smaller than 5 cm who do not have cirrhosis. Orthotopic liver transplantation offers several advantages, including eliminating the possibility of local recurrence and removing the cirrhotic liver. In patients who are not candidates for surgery, tumor ablation with transcatheter arterial chemoembolization, brachytherapy, stereotactic body radiation therapy, or radiofrequency ablation can prolong survival or potentially reduce tumor size (Cicalase, 2019).

Systemic Treatment Options for HCC

Sorafenib, an oral multikinase inhibitor, was the only approved systemic therapeutic agent until recently, when several new drugs were introduced. In August 2018, the U.S. Food and Drug Administration approved lenvatinib, an oral multikinase inhibitor, for first-line treatment of unresectable HCC based on the phase III REFLECT trial. Dosing is 12 mg once daily, and the most common side effects ( are hypertension, diarrhea, decreased appetite, and decreased weight. Its side-effect profile is similar to sorafenib, although the incidence of palmar-plantar erythrodysesthesia is higher with sorafenib.

Nivolumab and pembrolizumab are approved as second-line therapies. In May 2019, ramucirumab was approved as monotherapy for those with alpha-fetoprotein levels greater than 400 and previously treated with sorafenib.

Supportive Care

Patients with HCC need careful monitoring with detailed assessments. Ongoing baseline liver function and blood count tests are necessary, as is prompt symptom management. Some patients may be sensitive to opioids and benzodiazepines because of poor metabolism or fluctuating kidney or hepatic function. Preventing opioid-induced constipation is important for all patients, but especially those with encephalopathy, which may be worsened by constipation. Consider prescribing lactulose with a goal of two to three bowel movements per day.

Fluid volume status must also be monitored carefully. Fluid overload is best managed with spironolactone and furosemide and potentially reduced sodium intake because large-volume paracentesis can result in renal decompensation and worsening encephalopathy. Providers should consider an early referral to palliative care program.

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