Second-line treatment options for hepatocellular carcinoma

Aug. 08, 2020

Tanios S. Bekaii-Saab, M.D. is a professor at the Mayo Clinic College of Medicine and Science, leader of the Mayo Clinic Cancer Center Gastrointestinal Cancer Program and consultant at Mayo Clinic in Phoenix, Arizona.

Editor's note: This interview was originally published in OncLive on July 17, 2020, by Erica DiNapoli. It has been updated and is shared here with permission from OncLive.

The emergence of novel agents in the hepatocellular carcinoma (HCC) treatment paradigm in recent years has somewhat complicated treatment and sequencing decisions, according to Tanios S. Bekaii-Saab, M.D., but as more phase 3 data come to light, navigating among the options available will become easier.

HCC, the most common type of primary liver cancer, occurs most often in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection.

Curative, first-line systemic treatment options for HCC include atezolizumab and bevacizumab. These are becoming the standard of care.

In 2008, the multikinase inhibitor sorafenib became available for late stages of HCC. Sorafenib improves overall survival and disease-free survival, and is the standard of care for advanced HCC.

There are a number of second-line treatment options that arrived after the introduction of sorafenib. Today, the preferred options in the second-line setting to optimize care in our patients with HCC should the disease progress past initial treatment include:

  • Regorafenib; a once-daily, oral multikinase inhibitor. In April 2017, regorafenib was approved for use in patients with HCC who were previously treated with sorafenib. The most common adverse reactions with regorafenib are hand-foot skin reaction, hypertension, asthenia/fatigue and diarrhea.
  • Cabozantinib; a once-daily, oral multikinase inhibitor. In March 2019, cabozantinib was approved for use in patients with HCC who were previously treated with sorafenib. The most common adverse reactions with cabozantinib include palmar-plantar erythrodysesthesia syndrome, hypertension, fatigue and diarrhea.
  • Ramucirumab; can be prescribed if your patient's alpha-fetoprotein is ≥400 ng/mL. However, ramucirumab is less preferred in patients previously exposed to bevacizumab.
  • Nivolumab +/- ipilimumab and pembrolizumab; also available, strictly based on U.S. Food and Drug Administration approval. Based on recent negative data, and uncertainties regarding their utility following progression on atezolizumab, these would not be recommended options.
  • Sorafenib or lenvatinib; could move to second-line treatment, although at this point in time, there isn't enough data available to support either of those agents beyond their indication in first-line treatment.

"Now, how do you choose between them? There are not much data to inform you," said Dr. Bekaii-Saab. "Some folks have been favoring regorafenib, while others favor cabozantinib. I think you're justified to use one or the other, but these would be the two agents of choice, following atezolizumab plus bevacizumab. There's one pathway, I should say, for patients who may not be eligible for atezolizumab plus bevacizumab. Let's say someone gets exposed to lenvatinib or sorafenib in the first line, the second line is going to be wide open for all these options. However, those patients will become a rarity. We're going to do everything possible to expose our patients to first-line atezolizumab plus bevacizumab because of the strength of the data.

"That's how I look at the landscape, in a simplified way with this cluster of agents, until we see more data from ongoing phase 3 studies. The challenge, of course, is how do we study second line at this point in time following atezolizumab plus bevacizumab? This is going to be our next clinical challenge and a focus for more research."