Managing AEs With Pembrolizumab and Lenvatinib

Bradley Monk, MD, FACOG, FACS: Let me ask you some quick practical questions, and then we’ll move on. There are some adverse reactions that are pretty clear—hypertension for lenvatinib, thyroid for pembrolizumab—but there are some that overlap. Let’s say diarrhea. Both medications cause diarrhea, certainly, as well as immune-related colitis like the oral anticancer therapy. Remember fatigue and GI [gastrointestinal] toxicity. Vicky, Nicoletta, or any of you, how do you sort out diarrhea as to whether it’s pembrolizumab related or lenvatinib related? Does anybody want to speak up?

Nicoletta Colombo, MD, PhD: It depends on the presentation of diarrhea. The most important thing is to treat diarrhea, so you’ll have to treat the patients. In terms of your question, which was about which drug you would stop in case of diarrhea, this is quite difficult to sort out because, as you know, lenvatinib has diarrhea quite often. On the other hand, to think of colitis and such important adverse effects, if the patient has diarrhea, I would possibly first think of lenvatinib and then the earlier drug. I don’t know. This is just a guess. Vicky, what do you think?

Bradley Monk, MD, FACOG, FACS: I ask hard questions. If it was easy, I wouldn’t ask it. Go ahead, Vicky.

Vicky Makker, MD: It is a hard question, and it’s often hard to tease out. You’re absolutely correct, Nicoletta. The degree of diarrhea can sometimes help you. Is it large volumes of watery, profuse diarrhea? Is there cramping, bleeding, mucus production, etc? Perhaps this is more of a colitis, or if it’s more like 2 or 3 small loose bowel movements, then may be more lenvatinib. Sometimes where in the cycle the diarrhea comes on can be helpful. If it’s in the middle of a cycle, then perhaps it may be the lenvatinib. Hold the lenvatinib, and see if it improves. If it’s at the beginning of the cycle, the general approach that I use is that I hold both and do my due diligence and work-up to see if we can figure out what it is, but it’s sometimes really challenging.

David O’Malley, MD: Vicky, you said something early on, which is that these symptoms often present in those first 2 cycles. Often with diarrhea, we will see it present later, but usually, if it’s in the first 2 cycles, you’d know what the patient’s baseline is on lenvatinib. If you have a significant change beyond those first 2 cycles, then you have to start thinking that it’s I/O [immuno-oncology] associated. The problem for me is when it’s in cycle 2 when you’re pretty sure it’s from the lenvatinib, but you’re a bit worried. When you hold lenvatinib, the diarrhea should improve in a day or 2, to Brad’s point earlier. If I don’t see it improve, I start steroids right away or potentially bring them in for a more intensive work-up.

Bradley Monk, MD, FACOG, FACS: Beautiful. That’s really helpful. Imaging has also really evolved over the last decade or so for the work-up for pneumonitis. Not every cough is pneumonitis, but a chest x-ray CT scan will not solve that. The findings on CT scan for colitis are pretty pathognomonic because of the inflammatory response. A patient can have an abdominal CT scan and pelvis CT scan, which is pretty helpful. As you know, almost every ER [emergency department] has a CT scan in the ER, so if you’re having difficulty figuring things out, such as whether this cough is COVID-19, an upper respiratory tract infection, or immune-related pneumonitis, or whether the diarrhea is food poisoning, lenvatinib, or colitis, the CT scan can sort that out.

David O’Malley, MD: Let me challenge you on that, Brad. If you really want to make your patients mad, take lenvatinib associate diarrhea and give them oral contrast.

Bradley Monk, MD, FACOG, FACS: Let’s talk about that. I get it, you live in Columbus, Ohio, but in the modern era, we really don’t use oral contrast anymore. We give our patients a big glass of water. With the current imaging techniques, oral contrast doesn’t add much, believe it or not. At least that’s what my body imagers tell me. This idea that oral contrast somehow has a role anymore is, respectfully, a misnomer, according to my radiology colleagues.

David O’Malley, MD: We’ll agree to disagree, but I appreciate that. For those pathognomonic first 2 cycles, if you have a ton of cramping or if you have bloody diarrhea, as Vicky said, that brings my suspicion that it is much higher I/O associated.

Bradley Monk, MD, FACOG, FACS: I love the passion of this robust discussion and having fun with my friends. I just wish we were in the same room together.

Transcript Edited for Clarity