Dose Reduction Is Frequently Employed With Cabozantinib in NETs

Jason S. Starr, DO, assistant professor of medicine and a hematologist/oncologist in the Department of Internal Medicine at Mayo Clinic, discusses his approach to dose reduction of cabozantinib (Cabometyx) in patients with neuroendocrine tumors (NETs).

In the phase 3 CABINET trial (NCT03375320), the starting dose was 60 mg daily, and 66% of patients required dose reduction. Because of this outcome and the importance of quality of life, Starr says he tends to start patients at a lower dose of 40 mg, close to the median average daily dose of 38.4 mg actually received on the trial, which reduces the rate of toxicity.

Adverse events (AEs) that can occur include fatigue, hypertension, diarrhea, asthenia, and rash. Starr evaluates the effect of AEs on quality of life and sometimes decides to dose reduce further, or in rare cases where patients have no AEs he may escalate to 60 mg.

Since the trial reported outcomes in a majority of patients who had dose reductions, the favorable efficacy outcomes with cabozantinib include patients receiving lower doses.

TRANSCRIPTION:

0:10 | Quality of life is paramount for my patients, from my perspective, when you're dealing with a chronic disease. With cabozantinib, I start patients across the board at 40 mg. Two-thirds of patients require dose reductions on the study. The...median dose on the study, was 38 [or] 40 mg. I don't know how they got 38, but 40 mg, so that's where I start, and that really helps me to manage AEs, because I don't overshoot, because invariably with this medication, you get fatigue, you get some hypertension, some high blood pressure, some diarrhea, some asthenia, we call it, which is not feeling like you want to do anything. We get a rash on the hands and feet. We get taste changes. So when I start at the 40 mg, I just see less of those.

But if I do see any AEs essentially affecting their quality of life, that's my gauge. Or the high blood pressure that I can't control very well, I'll do a dose hold, let things settle, and then determine, is this 40-mg dose even the right dose? Do we need to back you off? I've had patients where I backed off to 20 mg. The drug has a long half-life, so it allows for that, but it's very rare that I say, "Oh, you're doing so well on the 40 mg, let's go up to 60 mg, but I will in patients who maybe don't have any [AEs], which is super rare, essentially.

The FDA approved dose is 60 mg, but again, the two-thirds of patients having a grade 3 or higher AE, the two-thirds of patients requiring a dose reduction, tells me that 60 mg is probably a bit spicy. So in my mind, in my practice, the 40 mg is probably the sweet spot, if you will. The data reflected that, because the data that read out that we got was including the fact that the majority of patients had a dose reduction.