Sorafenib Following HCC Disease Recurrence

Anthony El-Khoueiry, MD:The next question is when a patient would be appropriate for the initiation of sorafenib. So, if we go back to the case that we just reviewed, this patient had recurrence of the disease roughly 2 years after surgical resection. And the recurrence was in the liver as well as with the presence of lung metastases. The patient, at that time, still had Child-Pugh grade A liver function—well-preserved liver function—a good performance status, and definite extrahepatic disease in the lung. This is a typical patient for the initiation of systemic therapy, and, currently, the only standard-approved therapy for first-line treatment of metastatic hepatocellular carcinoma is sorafenib. So, this patient met the classic indications for sorafenib.

Once we start sorafenib, the question becomes, “What kind of follow-up should be done and with what intervals?” In clinical trials, we generally follow patients every 2 cycles—every 2 months of therapy. That is usually our practice, to restage patients with imaging—whether CT scan or MRI, including chest, abdomen, and pelvis—at about every 2-month intervals after the initiation of sorafenib. Using AFP to determine progression is not something that we do routinely. We may obtain AFP because the trend of whether it’s decreasing or increasing may tell us what’s coming in the future, but it may not always correlate with the imaging. So, we largely rely on imaging to determine progression. But, again, a trend in AFP that’s increasing or decreasing may tell us a bit about prognosis and help us foresee what’s coming in the future.

Typically, patients who are on sorafenib tend to achieve what we call stabilization of the disease. So, objective response—defined by a partial response that’s more than 30% reduction by RECIST criteria—is quite rare and has been reported to be at about 2% of patients in the SHARP trial. We largely look for stabilization of disease. Another indicator of response that has been reported is a change in the enhancement of lesions in the liver. So, a decrease in the extent of enhancement is usually indicative of necrosis and the cytostatic effect of sorafenib, and is considered a positive sign. It is very important to be cautious when following patients on sorafenib not to abandon the therapy too early. For example, the appearance of small sub-centimeter or peri-centimeter liver lesions that may be enhancing without washout or not enhancing should not be considered a definitive sign of progression. If the patient is doing clinically well, they should be continued on sorafenib, and subsequent imaging should be done to verify whether the lesion is real and is growing to determine definitive progression.

The other pitfall that I tend to see is abandoning sorafenib just because of a progressively increasing alpha-fetoprotein level when the imaging continues to show stability of disease. I believe that would be a premature discontinuation of the therapy. I think it is critical to remember that, in the initial SHARP and Asia-Pacific trials that led to the approval of sorafenib, patients were kept on the treatment until both radiologic progression and clinical deterioration. So, the survival benefit is likely to be driven by continuation of the therapy until there is a real progression.

Transcript edited for clarity.

February 2014

• A 63-year old male with HBV
• ECOG=0
• Child-Pugh A; platelet count 230,000 cells/mcL
• Bilirubin 1.0 mg/dL; Albumin 3.5 g/dL
• CT scan revealed liver lesions, 1 is 2-cm; 1 is 5-cm both in the right lobe
• No extrahepatic disease
• Biopsy confirmed HCC diagnosis
• AFP=5400 IU/ml
• Tumors were resected with RO margin

August 2016

• Imaging showed recurrence in the liver, metastatic disease in the lungs
• Therapy was initiated with sorafenib 400 mg BID
• Therapy was well-tolerated

April 2017

• Radiographic progression with multiple lung metastases
• ECOG=0
• Therapy with regorafenib initiated at 160 mg
• Starting dose was well-tolerated, patient experienced some fatigue