Key Advances in Endometrial Cancer - Episode 8
David M. O’Malley, MD: Let’s move on to KEYNOTE-146, which I refer to as LEN-PEM because it gets a little difficult to say lenvatinib and pembrolizumab. Dr Vicky Makker reported the final analysis that was published in the JCO [Journal of Clinical Oncology], looking at and diving down into the different aspects of these patients. When we look at the final report, Vicky does a wonderful job describing that there is a difference between patients who have received prior chemotherapy for adjuvant vs patients who have just received carboplatin-paclitaxel for recurrent disease. Meaning: If they have recurrent or advanced disease, they get carboplatin-paclitaxel and then move right into lenvatinib-pembrolizumab compared with a patient who received carboplatin-paclitaxel as adjuvant and then recurs and gets the agents of lenvatinib-pembrolizumab.
In the total population of patients, we see a response rate, depending on the report, of about 37% to 38%. We see this 37% to 38% in the entire cohort of patients, which is just under 100.
Dr Makker does a wonderful job in the most recent report looking at the differences between patients who have been treated with carboplatin paclitaxel vs those who received adjuvant therapy.
This is very interesting. When we look at the population of patients, the patients who received carboplatin-paclitaxel and then went right into LEN/PEM [lenvatinib-pembrolizumab] had a response rate of 41%, while the patients who had previously received carboplatin-paclitaxel for adjuvant and local-regional disease as the adjuvant setting had a 57% response rate. When we add up the numbers, they’re slightly different because there’s another group of patients who had more than 1 prior therapy, and that group of patients is going to be a little lower. So the entire population is about 37% to 38%.
Those who went right from carboplatin-paclitaxel are at about 41%, while those who received previous adjuvant therapy are at 57%. What does that mean to me? That means I always quote to my patients 37% or 38% response rate. But if I take a patient who had received previous therapy of carboplatin-paclitaxel for adjuvant, their response rate is up to about 57%. This is a small group of patients. We need to see the confirmatory trial, which will hopefully be reported shortly to drill down into this answer.
The toxicity with LEN/PEM [lenvatinib-pembrolizumab] is real. You have all the associated I/O [immuno-oncology] toxicities, then you bring in lenvatinib. So let’s talk about the I/O–associated toxicities. We need to learn from our lung cancer and melanoma experts because they have so much more experience with these agents. When I discuss with a patient the toxicity associated with pembrolizumab or other I/O agents, I talk about a 30% to 40% chance of an I/O-associated toxicity, which would require me interrupting treatment and potentially giving steroids. Of that 30% to 40%, 5% to 10% will have toxicities that will potentially require hospitalization.
We’ve gotten better at managing these toxicities, so I suspect that number is closer to 5% now. But within that population, we have about 1% to 2% of patients who will have life-threatening or life-altering toxicities. Somebody becoming a type 1 diabetic or losing their function of the pituitary is life altering. That’s rare. But if it occurs, it is obviously life altering. Combining with that lenvatinib, what are the other challenges with lenvatinib? Hypertension, diarrhea, some skin changes can be an issue, hair changes, some whitening of the hair. The ones I worry about are the diarrhea and the hypertension.
These are patients who I give the antidiarrhea directions to and make sure they have the medications at home. We also give them the prescription. I have colleagues who make them fill a prescription so they have something at home while we give them the prescription, because we always know these high blood pressures occur on the weekend without our usual team in place. We give the patient a prescription if they need them, and we make sure we have them monitored closely. What else have we done? We’ve instituted weekly videoconferencing with the patients. One thing that has come out of the COVID-19 [coronavirus disease 2019] era is the ability to perform videoconferencing.
We now have once-a-week videoconferencing for the first cycle and potentially second cycle to make sure we’re on top of these toxicities. You have to remember that about 80% of patients on lenvatinib-pembrolizumab will require dose reduction. Some people would argue 88% if you include the dose interruptions. The usual starting dose is 20 mg. That’s the recommended dose. Personally, 20 mg can be a challenge because they get only two 10-mg tabs.
If you dose reduce, you’re going right from 20 to 10 mg, and I’m telling you that 70% to 80% are going to be dose reduced. What we do is order the 18 mg. That comes with a 10-mg tab and two 4 mg tabs. I feel much more comfortable with a 10% adjustment from 18 to 20 mg. It’s unlikely that we’re impacting efficacy. Then when that patient needs to be dose reduced, I can dose reduce according to the package insert down to 14 mg, and if I need to go down to 10 mg, they still have that option.
Transcript Edited for Clarity