AGA: Consider Individualized Approach for Systemic Therapy in HCC

Systemic therapy for hepatocellular carcinoma (HCC) should generally be reserved for patients ineligible for curative surgery or locoregional therapy who have adequate liver function, the American Gastroenterological Association (AGA) said in a new clinical practice guideline.

While noting mostly low-quality evidence, the guideline offers first- and second-line options in the unresectable/metastatic setting and recommends against adjuvant systemic therapies in the curative setting and for patients undergoing transarterial chemoembolization (TACE), reported Grace Su, MD, of the University of Michigan in Ann Arbor, and colleagues, writing in Gastroenterology.

“Deciding the best treatment for your liver cancer patient is not a one-doctor decision,” said Su in a press release. “Our hope is that this new guideline empowers GI doctors to build relationships with multidisciplinary providers, such as oncologists, that will ultimately determine the best individualized treatment for their patients.”

HCC incidence has tripled since 1980. Cases often present at intermediate or advanced stages, where curative options such as ablation or surgery are no longer possible, Su’s group noted.

They added that in recent years, “a multitude of new systemic options have arisen, including molecularly targeted therapies and immunotherapies, which have shown promise in HCC.”

The guideline was divided into therapy suggestions for four patient groups: first-line treatment for HCC in patients with preserved liver function; second-line treatment for individuals with disease progression or intolerance to first-line systemic therapy; systemic therapy in patients with poor liver function; and systemic therapy for HCC in the adjuvant therapy setting.

First-line Treatment in Patients With Preserved Liver Function

Atezolizumab (Tecentriq) plus bevacizumab (Avastin) was suggested as a first-line treatment over sorafenib (Nexavar) for patients not eligible for locoregional therapy or resection or with metastatic disease.

The IMBrave150 trial found intravenous atezolizumab plus bevacizumab administered once every 3 weeks was superior to twice-daily oral sorafenib in HCC patients with preserved liver function naïve to systemic therapy.

Su’s group added that patients should have an endoscopic evaluation and be treated for esophageal varices before treatment, since bevacizumab may cause gastrointestinal bleeding.

For patients not eligible for atezolizumab plus bevacizumab, the guideline suggested lenvatinib (Lenvima) or sorafenib over no therapy at all. They noted that patients valuing delayed disease progression over increased adverse events “may reasonably choose” lenvatinib over sorafenib. However, those valuing blood pressure control over “adverse skin reactions” might prefer sorafenib over lenvatinib.

Second-Line Treatment

The authors noted that there are currently “no comparative studies among approved second-line therapies to guide decision making on a first option for second-line treatment” and suggested that patients with disease progression on sorafenib may choose either cabozantinib (Cabometyx), pembrolizumab (Keytruda), or regorafenib (Stivarga) over no systemic therapy. Patients with alpha fetoprotein >400 ng/mL may use ramucirumab (Cyramza) as well.

However, they added that patients who value avoiding adverse events associated with these treatments over a modest reduction in mortality (1-3 months) “may decline” any of these therapies.

Therapy in Those With Poor Liver Function

Su’s group does not suggest use of sorafenib, although patients who are not terminal patients (Child-Turcotte-Pugh class C), and value an “uncertain reduction in mortality” over the potential harms may “reasonably select” to use sorafenib.

Adjuvant Systemic Therapy

For patients undergoing curative surgical resection, curative local ablation or TACE, the authors do not suggest adjuvant sorafenib therapy. Bevacizumab therapy is also not suggested for patients undergoing TACE.

The AGA panel acknowledged that all the recommendations were conditional and based on low- to very low-quality evidence. They added that few biomarkers exist on guiding patient selection for different regimens. Also, clinical trials used to formulate these guidelines were limited to patients with preserved liver function, while patients with Child-Turcotte-Pugh C cirrhosis have no options for systemic therapy.