Case Presentation: 63-Year-Old Man With Advanced HCC

Michael A. Morse, MD, FACP:This is a 63-year-old man who is known to have chronic hepatitis B and he’s being appropriately screened. At that time, he’s found to have 2 hepatic lesions. Laboratory tests suggest that he has Child-Pugh A liver function, and he is now presented with the question of how to manage the disease.

On further evaluation he’s found to have an AFP [alpha-fetoprotein] of about 300, and that he does have Child-Pugh A liver function. The question at that point is regarding the best management of the disease. Appropriately here with a high AFP, the imaging finding, this is clearly a hepatocellular carcinoma. So he went to a surgical resection. The things we look for at the time of surgery are whether there’s vascular invasion—there was none—and how many lesions—there were 2. The sizes were 5 cm and 2 cm. There is no known benefit from adjuvant therapy in these patients, so he was monitored. Unfortunately, he was found to have recurrent disease. He had 1 new liver lesion and then also had pulmonary metastasis as well. His AFP, which had normalized after the surgery, had increased again. Clearly, he’s having a recurrence of disease. I don’t think this is something that needs to have a biopsy to prove recurrence with the rising AFP at this point.

Then, since he still had Child-Pugh A disease, he was offered the opportunity to take systemic therapy given there was extrahepatic spread. He proceeded to lenvatinib. In terms of lenvatinib, we’ll talk about some of the adverse effects of this whole class of drugs later. He tolerated it with some fatigue and some diarrhea, but he initially did have a response with some decrease in his tumor marker and also in the extent of disease. But unfortunately, as is often the case, he began to have more progression with further pulmonary metastasis and rising AFP, now above 400.

He still had a good performance status, PS 0, his Child-Pugh classification was still A, and so the opportunity for second-line therapy was discussed with him. Cabozantinib was started at the standard dose of 60 mg, which he did tolerate but eventually developed some diarrhea. Because of that, had a dose reduction to 40 mg. He continued on it and was noted to have partial response. As is often the case, eventually he had progression of disease after the initial clinical benefit.

I’m often asked about what the prognosis is after people have had surgery and then certainly if they have recurrent disease, what the future’s going to look like for them. After surgery, the most important feature is whether there’s vascular invasion. Also, the size of the tumor is important as well. In his case, although the range is quoted to be about a 40% to 70% 5-year survival, in reality his is about a 60% 5-year survival. Unfortunately, he had progression of disease, and at the point we’re now talking about him getting cabozantinib, the median survivals are about 8 to 11 months.

Transcript edited for clarity.

Case: 63-Year-Old Male with R/R mHCC

February 2018: Initial presentation

• A 63-year-old man with chronic HBV infection referred for further imaging studies based on suspicious findings during routine ultrasound for HCC

Initial Clinical Workup

• AFP: 300 IU/mL
• Child-Pugh A
  • Platelets: 210,000 cells/mcL
  • Bilirubin: 1.2 mg/dL
  • Albumin: 3.6 g/dL
  • INR: 1.1
  • No hepatic encephalopathy
  • Ascites not present
• Imaging: CT revealed 2 lesions in right hepatic lobe (2cm, 5cm); no extrahepatic disease; no cirrhosis; no portal hypertension
• BCLC: B
• PS: 0

Treatment

• Patient underwent right hepatectomy; negative margins; no vascular invasion
• AFP: WNL

December 2018

• On routine follow-up, imaging showed new lesion in left hepatic lobe (~2.3cm)
• Chest CT showed 3 small lesions (<1cm) in upper left lobe of lung
• Patient started on lenvatinib 12 mg QD; experienced moderate diarrhea and fatigue
• Imaging at 3 and 6 months showed partial response
• AFP: 100 IU/mL
• BCLC: C
• PS: 0

August 2019

• Routine follow-up blood sample reveals AFP 450 IU/mL
• CT scan showed progression in the lung and 2 new liver lesions; remains Child-Pugh A
• Patient started on cabozantinib 60 mg QD
• Patient developed grade 2 diarrhea; dose-reduction to 40 mg QD
• Imaging at 3 months showed stable disease
• Imaging at 6 months showed partial response