Case 2: Clinical Experience with the Tucatinib Regimen


A panel of experts review the tucatinib regimen including adverse effects to keep an eye on.

Joyce O’Shaughnessy, MD: I want to go around the Zoom call and offer some experiences that you’ve had in your patients with brain mets [metastasis] with the tucatinib triplet, both with regards to efficacy as well as any safety challenges or toxicity that you have noticed and developed some strategies for. How about you, Mark?

Mark Pegram, MD: I’ve had some success with tucatinib, including CNS [central nervous system] metastasis. It’s often been in conjunction with stereotactic radiation [SRS] therapy in most cases. It’s a well-tolerated regimen in general. Diarrhea is the most common issue that you may need to adjust the dose or co-administer medications to mitigate against diarrhea. You have to monitor the LFTs [liver function tests] and sometimes you have to do dose modifications based on transaminase elevation with tucatinib. In the case of tucatinib, you do have to monitor concomitant medication use by the patients who are being treated with other conditions because there are other drug classes that use CYP3A4, CYP2C8, or P-glycoprotein. Any drugs that use those pathways, you would have to look out for drug-drug interactions with tucatinib. That’s the only other issue that’s come up that takes a little bit of time to do a quick search to make sure that the ConMed list is acceptable with tucatinib.

Joyce O’Shaughnessy, MD: I’m keeping my oncology pharmacists busier these days than I have in the past. Thank goodness for them. They have these wonderful databases and they can look at the med list quickly, which is essential these days, not just for tucatinib but for our agents that we’re using these days. Bill or Adam, what kind of experiences have you had with the tucatinib with the patients with brain mets, any toxicity issues?

William Gradishar, MD: I’m not sure that I’m convinced that I’ve seen somebody that had regression of brain mets. They’ve maintained stable disease. I’ve seen systemic regression of disease and I would echo what Mark said about toxicity. The most common thing we’ve got to do is reduce the dose of capecitabine more than tucatinib, because of the GI [gastrointestinal] symptoms, preferentially first fiddling around with capecitabine before changing the tucatinib.

Joyce O’Shaughnessy, MD: That’s my experience, too.

Adam Brufsky, MD, PhD: I had a woman who had progressed with whole brain radiation as well as SRS, and we were running out of stuff to do. We put her on tucatinib and she did have [some] regression..... [but] stability otherwise. The issue is that what do you do now if you have one or two of the mets progress, but the rest of them stay stable, which is what happened in this patient. We gave her SRS to those lesions and continued her on tucatinib. The only thing that I found initially, and my nurse practitioners brought this to my attention, we actually thought we were overdosing the patients on capecitabine. We happened to see more PPE, the plantar-palmar erythrodysesthesia than we normally do. It’s like Mark said, we have these drug interactions and this other stuff, these CYP34A inhibitors, and we don’t realize it because we’re not oncology pharmacists. We have to have a lot of caution when we give these together, and I find myself reducing the capecitabine as opposed to tucatinib.

Joyce O’Shaughnessy, MD: I have a couple of people that I have in mind right now, with brain mets. Three of these women that are coming to mind right now, don’t have any disease outside the brain but they, unfortunately, have multiple brain mets. They’ve had SRS, one had to have whole brain, it was so many, but they are doing well on the triplet. I’ve also had to dial back on the CAPE [capcapecitabine] for pretty much all of them, but they’re doing super well. It takes a little bit of time to get the right dose as we do anyway with capecitabine. CAPE is a little bit, takes a little while to work out the CAPE, doesn’t it, for everybody, but these women are doing really well, very durable benefit from this triplet. That’s the big issue is their brain. So I am impressed with the brain activity of that triplet.

Transcript edited for clarity.

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