Impact of Lenvatinib-Pembrolizumab on Clinical Practice in Advanced EC

Vicky Makker, MD: In terms of my experience with this regimen, not only after the results of KEYNOTE-146, but also Study 309, or KEYNOTE-775, I have to say that my experience has encouragingly been comparable in the real world to what we saw on both the clinical trials. We’ve seen that the adverse effect profile has been comparable. The lessons that we learned from KEYNOTE-146 were very helpful as we treat patients not only on KEYNOTE-775 but also in the real world. Developing comprehensive management strategies so that the whole team is well-versed on the adverse event profile, and then developing rational ways to care for patients comprehensively, has been very helpful to us. We have seen that the adverse events have been consistent with what we saw on both of the studies, which has been encouraging.

It’s important to develop thorough management strategies. I cannot state enough the importance of patient education, staff education, and team education so that everyone understands how these agents work and what potential adverse events can come. If this combination is approved for patients who have mismatch repair-deficient or microsatellite instability-high endometrial cancers, it will give us another treatment option in addition to checkpoint inhibitors as monotherapy. At that point, it will warrant a very thorough discussion with our patients regarding the efficacy and potential adverse effects of these therapies. It will also warrant that clinicians be mindful of the patient’s disease status. Does the patient have bulky disease vs disease that is low volume? Also, what is the pace of their disease? Is it indolent or is it rapidly progressive? Keeping in mind the patient’s performance status, organ reserve, and medical comorbidities will be important as they ponder this combination vs checkpoint inhibitors as monotherapy for patients who are mismatch repair-deficient or microsatellite instability-high.

Shannon N. Westin, MD, MPH, FACOG: I’ve been excited to have an FDA-approved regimen like lenvatinib and pembrolizumab available for my patients with microsatellite-stable disease because we previously had minimal options for this patient population. I’ve used it quite a bit over the last year or two since its approval. The most important thing is setting expectations with patients. This is a doable regimen. We’ve seen the data that Dr Makker presented, that there were high levels of grade 3 and 4 adverse events, but that doesn’t mean they can’t be mitigated. The exciting efficacy data she showed us are worth fighting for. We like to keep in touch with those patients very closely, make them aware, from the beginning, of the potential adverse events they may experience, and make sure they know to get in touch right away.

We’ve started trying to be as proactive as possible. The critical adverse events we see most commonly are hypertension, fatigue, mucositis, diarrhea, and rash. There are other adverse effects, which she’s gone through in great detail, but those are the critical ones that we try to get out in front of. Make sure patients have a monitor to check their blood pressure. We have even started giving them a prescription for blood pressure medications ahead of time, so they can have it at the ready and don’t need to call us to get that script. We want them to call us before they start it, but we at least have them ready to go with that. They’re monitoring closely, they know what levels we’re looking for, and they know that they have something to start taking if they need it.

From the standpoint of the diarrhea, we do the same thing. We make sure they have an antimotility agent available to them. They know the minute they start having diarrhea, they can start taking that, and they should reach out to us if they need other strategies so that we can get ahead of it. The goal is not to get to that grade 3 toxicity. The goal is to act at grade 1 and prevent it from getting so bad. We also act quickly with rash and mucositis. The minute we start seeing a little bit of a rash or the patient has some soreness in the mouth, we act. We give them things to mediate that and help reduce the severity of that. We take fatigue seriously. We try to get patients active from the beginning, because we’ve found that exercise and activity can really help combat that fatigue. But if they’re not up to it, that’s OK, we do a dose break. We give them a break, a week or two off, and we may consider reducing the dose if we need to.

The bottom line for this regimen is to be aware of the toxicities that are possible, make sure the patient’s aware, and then have a really good mechanism of communication, where you try to prevent what you can, and then have options at the ready to intervene with things that you can’t prevent. You don’t want to get super behind with these adverse events and then have a patient that says, “I don’t want to do this; I can’t do this.” Nobody wants to get there. These outcomes are too good, with 70% of patients getting some kind of clinical benefit. You don’t want your patient to lose that opportunity for clinical benefit because of adverse events. Those are some of the strategies that we’ve employed at our institution to try to let patients stay on this regimen and do well.

Right now, the indication for this regimen is strictly for patients who have microsatellite-stable disease. We’re seeing some interesting activity across all tumors, so we may see that indication gets expanded to patients who have a microsatellite instability-high tumor. This becomes more of a discussion with the patient and understanding there’s a proportion of patients who aren’t going to need that combination regimen. Perhaps look to start the single agent of the pembrolizumab alone and then follow closely. If you’re not getting the clinical benefit that you would expect, perhaps add the second drug, add lenvatinib, to see if you can get better benefit. Right now, that’s how I would foresee my clinical practice incorporating the combination regimen for patients who have microsatellite instability-high disease.

Transcript Edited for Clarity