Regorafenib in Advanced HCC

Anthony El-Khoueiry, MD:Upon progression, the patient still had a well-preserved ECOG performance status of 0 and was then started on regorafenib at a full dose of 160 mg/daily, which he tolerated well except for mild fatigue. So, the next question becomes a matter of what to do upon the progression of a patient who was on sorafenib and then had progression of disease in the lungs that was verifiable on imaging. Until recently, we really had no standard second-line therapeutic options post progression on sorafenib. And now, with the RESORCE trial, we have evidence that patients who had verifiable radiologic progression on sorafenib, who had tolerated a minimum dose of 400 mg/daily for the last 20 of the 28 days that they were on therapy, and who were randomized subsequently upon progression to regorafenib versus placebo had a survival benefit.

Patients had improvement in overall survival and progression-free survival, as well as a response rate around 6% to 7%. The RESORCE trial showed a benefit from regorafenib post progression on sorafenib in all endpoints. The other caveat is that the RESORCE trial was restricted to patients with well-preserved liver function and Child-Pugh grade A cirrhosis. So, they had verifiable progression, they had tolerated sorafenib reasonably well, and they had well-preserved liver function. Based on the RESORCE trial, these would be the patients that would meet the indication for the usage of regorafenib post-progression on sorafenib, and this patient certainly met those criteria.

The clinical experience with regorafenib for hepatocellular carcinoma is just starting. Based on the RESORCE study, patients were started on the full dose of 160 mg/daily. When reviewing the adverse event profile, it is interesting to note that the therapy was largely well tolerated. About 40% to 50% of patients required dose interruption or reduction, so this is something that treating physicians should be aware of. But the initiation of 160 mg/daily was certainly feasible, and liver function appeared to be well-preserved. So, the rate of significant grade 3 and grade 4 adverse events related to liver function, such as elevated bilirubin or ascites, was really no different between the regorafenib arm and the control arm of best supportive care or placebo. I do tend to start patients on the full dose and do a dose reduction as appropriate.

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