So I am here with Dr. Flora Backus, and she's going to tell us a little bit about what she presented.

Hi.

So, yes, I had the honor to present Energy GY020, which, as a reminder, was a comparison trial in a high-intermediate-risk, mismatch-repair-deficient endometrial cancer population in early stage, stage 1 and 2.

And so what we compared was vaginal brachytherapy with or without pembrolizumab.

And then for some of the patients who were stage 1B grade 3 or stage 2, they were also allowed to have external beam radiation.

So with that, while it was an interesting trial, it did not show any difference.

So we will not be adding pembrolizumab for patients with early-stage, high-intermediate-risk, mismatch-repair-deficient endometrial cancer, as pembrolizumab did not change the outcomes.

I mean, this is a

Let's say it's recurrent now, just like Dr. Magellan's case, where she used a CDK4-6 inhibitor.

So I think probably the time when you could have made that decision would have been at the time when she had her mass resected.

I mean, personally, I probably would have biopsied the lymph node and it may have done nothing if you've resected that.

And I may consider radiation if you're worried about positive margins.

And then see what happens.

Because these patients may not need it.

And now she's committed to it and has obviously toxicity for it.

What about some of these other biomarkers? Do you ever test for ESR1, which is used in breast cancer, PIK3K, AKT, P10, anything else that you guys are, CCNE1, anything else you guys are testing for? Talk about even clinical trials.

Let's say it's recurrent now, just like Dr. Magellan's case, where she used a CDK4-6 inhibitor.

So I think probably the time when you could have made that decision would have been at the time when she had her mass resected.

I mean, personally, I probably would have biopsied the lymph node and it may have done nothing if you've resected that.

And I may consider radiation if you're worried about positive margins.

And then see what happens.

Because these patients may not need it.

And now she's committed to it and has obviously toxicity for it.

What about some of these other biomarkers? Do you ever test for ESR1, which is used in breast cancer, PIK3K, AKT, P10, anything else that you guys are, CCNE1, anything else you guys are testing for? Talk about even clinical trials.

clap

after I'm done.

So let's start.

So I was tasked with these objectives.

So we're going to be discussing the endometrial cancer molecular subtypes, review the implications for prognosis and therapeutic decision-making.

We'll go over first-line treatment for advanced and recurrent endometrial cancer and look at some of the biomarkers for immune checkpoint inhibition.

and then some ongoing first-line studies in DMMR endometrial cancer.

So we can't really say

clap

after I'm done.

So let's start.

So I was tasked with these objectives.

So we're going to be discussing the endometrial cancer molecular subtypes, review the implications for prognosis and therapeutic decision-making.

We'll go over first-line treatment for advanced and recurrent endometrial cancer and look at some of the biomarkers for immune checkpoint inhibition.

and then some ongoing first-line studies in DMMR endometrial cancer.

So we can't really say

was

not involved.

But a lot of those patients did not have a complete response.

And so there's actually a really interesting post.

I'm going to put a plug in here for one of our fellows, Julia Tilleth, I had a poster, and we have a group of about over 50 patients where we looked at the patients that still had a uterus in place and truly got, well, just regimen for metastatic disease.

We left the uterus.

Well, they had a beautiful response oftentimes outside the uterus in the omentum and the peritoneum.

Yeah, and I think Dr. Letterman's trial, they are all getting surgery afterwards, so I think it will also be helpful.

Backus.

Yeah, so I think it is important because we know that these tumors, especially that they can evolve over time.

We can see responses in one part and we can have something else that is persistent and that may be treated differently also.

We have so many more options now.

Repeating, I guess in a lot of situations, like if the patient was HER2 positive, I probably wouldn't repeat that.

But if she was negative, yes, I definitely think that repeating a biopsy can be helpful to have another option for treating these patients in the future also.

Dr. Powell, anything to add?

Dr. Backus? I struggle

Backus.

Yeah, so I think it is important because we know that these tumors, especially that they can evolve over time.

We can see responses in one part and we can have something else that is persistent and that may be treated differently also.

We have so many more options now.

Repeating, I guess in a lot of situations, like if the patient was HER2 positive, I probably wouldn't repeat that.

But if she was negative, yes, I definitely think that repeating a biopsy can be helpful to have another option for treating these patients in the future also.

Dr. Powell, anything to add?

Dr. Backus? I struggle

But sort of where you've landed and where you see your colleagues in, you know, clinical investigator oncology or gynecologic oncology landing in terms of how you, for practically purposes outside of trial, think through first-line therapy of metastatic disease in the MS stable and the MSI patient.

Yeah, I think it's going to be interesting because we were all very surprised, of course, when that data came out now over three years ago.

We were at that point, we knew how well the checkpoint inhibitors worked in mismatch repair deficients.

endometrial cancer and how poorly it worked in the proficient population.

So then when that data came out, when we combined it with chemotherapy and then continued with the immunotherapy maintenance in both those trials, that there was a benefit, not just in the mismatch repair deficient population, but also in the mismatch repair proficient population.

It wasn't as strong.

It wasn't a hazard ratio of 0.3, but it was somewhere between 0.5 and 0.7, which is still very respectable, a 30% to 50% reduction in the risk of recurrence for death.

What's your approach to these? And in what situation will you re-challenge like a patient who's done well, but then has one of these complications?

But sort of where you've landed and where you see your colleagues in, you know, clinical investigator oncology or gynecologic oncology landing in terms of how you, for practically purposes outside of trial, think through first-line therapy of metastatic disease in the MS stable and the MSI patient.

Yeah, I think it's going to be interesting because we were all very surprised, of course, when that data came out now over three years ago.

We were at that point, we knew how well the checkpoint inhibitors worked in mismatch repair deficients.

endometrial cancer and how poorly it worked in the proficient population.

So then when that data came out, when we combined it with chemotherapy and then continued with the immunotherapy maintenance in both those trials, that there was a benefit not just in the mismatch repair deficient population, but also in the mismatch repair proficient population.

It wasn't as strong.

It wasn't a hazard ratio of 0.3, but it was somewhere between 0.5 and 0.7, which is still very respectable, a 30% to 50% reduction in the risk of recurrence for death.

What's your approach to these? And in what situation will you re-challenge like a patient who's done well, but then has one of these complications?

So let's go ahead and get started.

Great.

Thank you for that nice introduction.

Welcome, everybody.

I hope you enjoy your lunch also.

So here are my objectives.

We're going to be talking about molecular subtypes, review the implications for prognosis and therapeutic decision-making, look at biomarkers for response to immune checkpoint inhibitors, talk a little bit about BRCA1,2 and HRD in endometrial cancer, and then talk about guideline-endorsed approach to the assessment of other clinically relevant biomarkers.

Let's say it's recurrent now, just like Dr. Magellan's case, where she used a CDK4-6 inhibitor.