Optimal Management of Relapsed/Refractory mHCC - Episode 5
Michael A. Morse, MD, FACP:Of course, it’s also important to emphasize the tolerability of a drug like cabozantinib. As a VEGF TKI [tyrosine kinase inhibitor], it has some of the same adverse effects as the other drugs in the class. The most common side effects were things like diarrhea, hand-foot syndrome, nausea, fatigue, and hypertension. But I found it to be very well tolerated. This is a classic example though of where a patient is started at 60 mg but required a dose reduction because of diarrhea.
This patient started at the full dose, which is completely appropriate for a patient with Child-Pugh A liver function. They started at 60 mg. However, because of toxicity, the dose was reduced to 40 mg. If you look at the CELESTIAL trial, 38% of patients were able to stay at the full dose, but 62% did require dose reductions. In terms of dose discontinuations though, it only affected 16% of patients.
There are some other considerations in patients taking cabozantinib. The first thing to understand is it has about a 99-hour half-life. As most people know from pharmacokinetics, it takes about 5 half-lives to be at steady state. What that means is the adverse effects begin at approximately 2 weeks. Some of them occur at 3 weeks, and some start at about 4 weeks. It’s important to either have the patient come back to clinic, or call them, or have them call in at about 2 weeks to see how they’re tolerating the drug.
The second consideration is that there can be interactions with drugs that target CYP3A4. If a patient is getting an inducer of CYP3A4, they may need a higher dose of cabozantinib. If they’re receiving a drug that inhibits CYP3A4, they may need to start at a lower dose of cabozantinib.
Many of the patients I see have Child-Pugh B. In the case presented, this individual had Child-Pugh A. But in having to deal with somebody who has Child-Pugh B, it’s important to start the dose of cabozantinib at 40 mg because there can be higher toxicity if you start at 60 mg.
Transcript edited for clarity.
Case: 63-Year-Old Male with R/R mHCC
February 2018: Initial presentation
Initial Clinical Workup