Endometrial Carcinoma Treatment Advances - Episode 4
Practical perspectives on the optimal use of combination lenvatinib-pembrolizumab in endometrial cancer.
Brian M. Slomovitz, MD, MS, FACOG: Pembrolizumab and lenvatinib changed the world. Their implementation into the treatment of endometrial cancer was game changing. FDA indications allow pembrolizumab and lenvatinib for patients who fail prior systemic therapy. It doesn’t require a full regimen of chemotherapy. It doesn’t even require chemotherapy. Patients can fail hormonal therapy. But it’s a second-line trial, so those patients can be included.
One issue with pembrolizumab and lenvatinib has been toxicities, leading to dose delay and dose discontinuation. The normal starting dosage of lenvatinib is 20 mg daily. We’ve found that several of those patients have required dose reductions in order to get an acceptable dose in. The starting dose is 20 mg. Some patients would likely benefit from starting at a lower dose. We’re performing studies to determine if that would yield the same efficacy as starting as 20 mg. As we know, some patients do well with a lower dose. If we started at a lower dose, we wouldn’t be sure we’re getting an adequate dose in to those patients who wouldn’t normally require a dose reduction. As far as discontinuations go, it does happen with this drug. We’re looking for mitigation strategies to limit that from happening.
The No. 1 adverse effect of pembrolizumab and lenvatinib that I’ve seen is hypertension. Lenvatinib can cause an elevation of blood pressure. When I prescribe pembrolizumab-lenvatinib, I look to manage the high blood pressure, or manage the blood pressure. In patients who are on antihypertensives, I encourage them to reach out to their primary care provider or the cardiologist who’s prescribing those drugs. This is to prepare them for lenvatinib, which may increase their blood pressure. For those who aren’t on antihypertensives, we monitor their levels closely and ensure that if they do develop a hypertension, we start them on an antihypertensive that will help manage symptoms.
Another common adverse effect we see is diarrhea. It’s sometimes difficult to determine which of the 2 drugs, pembrolizumab or lenvatinib, causes diarrhea. In my patients who developed diarrhea while on this regimen, my strategy has been to hold the lenvatinib to see if the diarrhea resolves. If the diarrhea stops, it’s most likely from lenvatinib. If it doesn’t resolve, then it’s most likely from pembrolizumab. Then we implement different strategies to limit the diarrhea based on the drug that caused it.
Transcript edited for clarity.