Exploring Immunotherapy Combinations in Endometrial Cancer - Episode 5
Experts in gynecologic oncology share insights on patient selection for lenvatinib-pembrolizumab in advanced endometrial cancer and discuss therapeutic sequencing through multiple lines of therapy.
Shannon N. Westin, MD, MPH, FACOG: How do you choose the right patient for the combination of pembrolizumab and lenvatinib? Obviously, if a patient has endometrial cancer or recurrent endometrial cancer, and they have had at least 1 prior line of therapy. We try to do it pretty early because it’s a regimen that can be tough, and you want your patient to be as healthy as possible. If they’ve had multiple lines of therapy, it may be a little harder, just like it is with chemotherapy, to give full-dosing strategies and manage those toxicities. You want your patient to have a good performance status and hopefully not too many priors.
With that being said, if you’re seeing a new patient who has already had multiple lines of therapy and has not yet had this option, I would not hold back. But if you’re ideally looking at who you’re going to choose, especially if we’re thinking about how we sequence treatments, trying to do this earlier in the treatment continuum is ideal—especially since we see a proportion of patients who are going to have a durable complete response. If you can get that several-year complete response for your patient early on, think of how many birthdays and events that patient can go to without going through other treatments, chemotherapies, and stress. That’s how I think about my patient selection.
Like I said before, we’re looking at patients who have microsatellite-stable tumors, and we’ll be watching closely to see if this indication is expanded. That’s one of the other key requirements. There aren’t any major contraindications for this regimen. For me, the performance status is critical. You want to make sure your patient is going to be able to tolerate this. I use a little caution if I have a patient who has hypertension who might be on multiple medications already. You really want to get that under control before you start pembrolizumab and lenvatinib because you’ll see that spike in the blood pressure [BP]. You want to make sure your patient is in the best possible space before you start that combination regimen.
Vicky Makker, MD: There are other aspects to consider with regard to patient selection. First of all, at the moment, the regimen has accelerated approval for MMR-proficient [mismatch repair-proficient] or microsatellite-stable endometrial cancers following prior therapy. Within this cohort of patients with endometrial cancer, which comprise the majority of the recurrent endometrial cancer disease space, I would consider the disease burden, the pace of the disease, the histologic and molecular profiles, and their prior therapy-free interval. Other important factors include the performance status of the patient. Ideally, the patient performance status should be 70 or greater. Patients should have adequate organ function. If they are hypertensive, they should be stable on a blood pressure regimen. They should be compliant with blood pressure assessments. It’s important for clinicians to try for optimal BP control—ideally 120 over 80 mm Hg or less—before the patients initiate therapy. You want to make sure they are stable on their blood pressure regimen. You don’t want to be making changes right before you initiate this regimen.
In my opinion, if patients have diabetes, it should be non–insulin-dependent diabetics who you consider for this regimen. If they have proteinuria, it should ideally be grade 1 or less. Patients should not have active autoimmune disease or chronic active hepatitis. They should ideally be free of cancer-induced cachexia or anorexia. Ideally, patients should not have a poorly controlled anxiety or mood disorder and should not display a history of noncompliance with regard to their prior therapies.
A communicative proactive patient is ideal for this regimen because it involves a lot of conversation and feedback with the clinical team. It’s ideal to have family involvement as well. Optimal management of patients with endometrial cancer on pembrolizumab and lenvatinib requires a multidisciplinary team approach where there is strong communication between the patient, medical oncologist, as well as nurses, PAs [physician assistants], NPs [nurse practitioners], social workers, and subspecialists. That has been the lesson we’ve learned along the way, and it has been profoundly helpful in the care of our patients.
Shannon N. Westin, MD, MPH, FACOG: I already referenced sequencing, but I’ll talk a little more about it. Right now, if you have a patient with newly diagnosed stage 3 or 4, or newly recurrent endometrial cancer, you’re going to look at chemotherapy for that patient. That’s going to be one of the first lines or strategies that you explore. For a patient who has a uterine serous tumor, you’re going to do HER2 testing and maybe add trastuzumab to the chemotherapy if it makes sense.
Conversely, if you have a patient with endometrioid-type tumors, you might consider utilizing an alternating hormonal strategy before chemotherapy. These are some of the considerations that you have. Once you’re getting into the second line, you’re going to make sure you do the microsatellite instability testing. If your patients have microsatellite-stable disease, that’s when you want to act and pursue the combination of pembrolizumab and lenvatinib. That is getting explored against chemotherapy, so it’s to be determined if it’s going to be a strategy that we use before chemotherapy. It’s certainly a very intriguing idea, but we’ll have to see what the data show from the trial that’s pursuing that.
Transcript Edited for Clarity