Managing Side Effects With Regorafenib in HCC

Ghassan K. Abou-Alfa, MD:Not surprisingly, the patient here got some side effects secondary to the regorafenib, which are not really different from those of sorafenib. As you can see, the patient has a grade 2 hand-foot syndrome and actually grade 1 hypertension. Appropriately so, the patient should be on an antihypertensive—the same way he was on antihypertensives for the sorafenib. As far as the hand-foot syndrome, the patient, with only 1 event on the grade 2 level, will be watched and monitored carefully and given supportive medications. But if it does really occur 1 more time, a little bit of holding and maybe dose reduction will be appropriate. I think, all in all, this does not worry me. This is expected, in a way, and definitely manageable.

Sorafenib and regorafenib appear, to many of us, as being the same drug, with only 1 fluorine atom added to the regorafenib. But I think this is really a much more complex comparison than that. Actually, regorafenib was built with that fluorine being added there on purpose, because it’s synergizing the drug in a different way. The story, however, is much more complex than that. We don’t know it yet completely, but we really know that there are certain targets that are more of interest for the use of regorafenib after sorafenib, like IGF and FGF.

And we know that this is a multikinase inhibitor, so it has an anti-IGF/anti-FGF factor as well. But more importantly, the story that we don’t know yet completely is that these targets are specifically of more interest and of more importance after progressing on sorafenib. In other words, what did sorafenib do or contribute to the tumor to make it more prone to regorafenib? That’s really what is a fascinating part of it, and many of us—including ourselves at Memorial Sloan Kettering Cancer Center—are working on that theory.

Transcript edited for clarity.

May 2016

• A 70-year old male with metastatic HCC involving the lung and bone confirmed by biopsy, experiencing mild bone pain
• ECOG=1
• Child-Pugh A
• Therapy was initiated with sorafenib at 400 BID
• Patient experienced grade 1 HTN and grade 1 hand-foot skin reaction, which was managed effectively

April 2017

• Documented radiographic progression
• Therapy with regorafenib at 160mg was initiated
• Patient experienced grade 1 HTN, grade 2 hand-foot skin reaction