HCC: Third-Line Treatments and Beyond

Richard S. Finn, MD:The fact that we’re talking about third-line options in advanced liver cancer is really remarkable. If you think about where we were not that long ago, we had sorafenib and only sorafenib for 10 or more years. Now, with all the positive data and the recent FDA approvals, we have more options and we are going to have to figure out how to sequence these. We are not going to have phase III data for patients as many of the studies are being compared to placebo, or they exclude prior agents, or the agents just weren’t available. I think if a patient is still eligible for systemic treatment, they’re well compensated, and they have a fair performance status, then certainly a clinical trial would be an option, or offering the treatment they did not have. So, for example, if they had sorafenib frontline and then received regorafenib at progression, upon progression on regorafenib, then it would be very appropriate to give them nivolumab. Or, if the sequence was sorafenib then nivolumab, then on progression on nivolumab, I would offer them regorafenib. The fact that we have drugs that have proven efficacy in liver cancer means that we need to follow our patients with imaging. We cannot wait until they have clinical progression, because if we do, they will not get access to the drugs that we have available that have been shown to improve survival.

In the past when we only had sorafenib, there was a tendency to just keep patients on drugs even though had radiographic progression. And now that we have other agents, again to optimize the possibility of giving patients a chance of receiving active drugs, we need to transition them probably sooner rather than later. Meaning at radiographic progression and not clinical progression. At clinical progression, they won’t be good candidates for treatment.

The recent approvals and positive studies in liver cancer are very exciting. It’s going to be an exciting year ahead as we await further phase III results. We expect the results from the phase III ramucirumab data as well as the frontline sorafenib versus nivolumab study. And we await further data with pembrolizumab in HCC, among other studies. This is an exciting time for us as investigators and for patients. The important thing for us to do probably now is to concentrate on identifying which patients benefit best from any given treatment, and how to optimally sequence these therapies.

Transcript edited for clarity.

February 2017

• A 59-year-old man with presented with RUQ pain and fatigue.
• PMH: Cirrhosis, HCV infection
• SH: lives alone, drinks alcohol daily (~15 drinks/week)
• ECOG, 0
• Laboratory findings:
  • AFP: 677 IU/mL
  • Platelets: 144,000 cells/mm³
  • INR, 1.7
  • Bilirubin: 1.8 mg/dL
  • Albumin: 3.9 g/dL
  • Hepatic encephalopathy: none
  • Ascites: mild
• Child-Pugh A
• Abdominal CT scan showed a large mass (8.6 cm) involving hepatic segments IV and VIII with portal vein infiltration, diffuse 1.0-cm to 1.5-cm nodules in the right hepatic lobe; 1.5-cm left portal vein thrombosis
• Surgical consult, unresectable based on tumor size and portal vein invasion
• Biopsy findings showed grade 3 hepatocellular carcinoma, marked fibrosis  
• The patient was treated with TACE; dynamic liver computed tomography at 1 month showed a partial response; repeat TACE showed no additional response
• The patient was started on sorafenib
• Imaging at 2 and 6 months showed a partial response with marked regression of the hepatic mass and smaller nodules.

February 2018

• The patient reports feeling fatigue, requiring rest during the day, but continues to work full-time
• CT of chest, abdomen, and pelvis showed new pulmonary nodules (2.0 cm and 3.1 cm) consistent with metastatic disease
• ECOG, 1
• He was started on regorafenib 160 mg daily
• After 2 weeks on therapy he developed grade 2 hand-foot syndrome which resolved after dose reduction to 120 mg daily
• After 3 months the patient has stable disease and improvement of symptoms