Initial Therapy Options for Liver Cancer

Richard S. Finn, MD:So, the case here describes that this patient had a marked response, a real partial response radiographically with tumor shrinkage. This is really what I would call an exceptional response to sorafenib. In randomized studies, sorafenib has a response rate in the single digits—2% to 3%. In more modern studies, that’s a little higher but still single digit. The fact that we’re seeing this response then is fairly unusual. Typically, patients have a slowing of progression. And in that setting, we are able to improve survival. Improving survival in a setting of HCC with the systemic treatments we have seems to be independent of imaging. So, even if this patient had stable disease at these imaging time points, we would still say that we would continue treatment if the patient’s likely benefiting. The fact that the patient has a significant response is intriguing and good for them.

Lenvatinib is a small molecule tyrosine kinase inhibitor that is currently approved in thyroid cancer and kidney cancer. And it has been shown to have activity in liver cancer. There was a large study, the REFLECT study, that was a noninferiority study in patients with advanced well compensated liver cancer comparing sorafenib with lenvatinib. The study was a positive study. It’s actually the first positive phase III study in frontline liver cancer in over a decade. And with that being said, lenvatinib was shown to be noninferior and not superior. However, if we look at some secondary endpoints, such as response rate, progression-free survival, and time to progression, lenvatinib did have superiority over sorafenib. The tolerability of lenvatinib is fairly typical for its class. Unlike sorafenib, it has a little higher incidence of hypertension but has less incidence of hand-foot skin reaction.

So, this patient, in my opinion, would be a candidate for lenvatinib. They are well compensated, they have a tumor that is Barcelona stage C, and we’ve seen in randomized studies that in a patient like this, it is another good option other than sorafenib.

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