Adjuvant CRT Yields No Survival Benefit in Advanced Endometrial Cancer

The long-running randomized NRG Oncology GOG-258 trial failed to identify an overall survival (OS) benefit with adjuvant chemoradiotherapy (CRT) versus chemotherapy alone in any subgroup of patients with locally advanced endometrial cancer, according to research presented at the Society of Gynecologic Oncology (SGO) annual meeting.

MedPage Today brought together three expert leaders in the field. Moderator Ursula A. Matulonis, MD, chief of the division of gynecologic oncology at Dana-Farber Cancer Institute in Boston, is joined by Kathleen Moore, MD, MS, a gynecologic oncologist at Stephenson Cancer Center at the University of Oklahoma in Oklahoma City, and Krishnansu S. Tewari, MD, a gynecologic oncologist at the University of California Irvine, for a virtual roundtable discussion. This last of four exclusive episodes covers their reactions to the final results from the randomized NRG Oncology GOG-258 clinical trial.

Following is a transcript of their remarks:

Matulonis: Hello, everyone. My name is Ursula Matulonis. I’m a medical oncologist from Dana-Farber Cancer Institute in Boston, Massachusetts. And I have the privilege and honor of being here today with two of my wonderful colleagues, Dr. Kathleen Moore from the University of Oklahoma, and Dr. Krish Tewari from the University of California Irvine. And we’re going to be talking about updates that were presented at the Society of Gynecologic Oncology 2023 annual meeting that just took place in Tampa, Florida.

So, next, we’ll talk about GOG-258. Daniela Matei, MD, did a great talk. She talked about, I think, when her daughter was born, and how the study was finishing when she was in college.

Tewari: Yeah, yeah, yeah. <laughter> That was great.

Matulonis: Yeah, so I think that’s sort of a statement in itself about just the length of time it takes to get trials off the ground, finished, and then presented. But impressions of the results of 258 — obviously, some of this has been upended by 018 and RUBY — but I think that potentially that incorporation of IO [immunotherapy] is not going to be for a while. Obviously, we’re waiting for the labels to change. But anyway, Krish, I want to start with you about impressions of 258 and what you thought of the OS data.

Tewari: Yeah, I think it speaks to your point. So, it’s a negative study. It started out negative when it was published in the New England Journal of Medicine; it was a negative study and it’s still negative. So, none of this surprises me.

In the original paper, they did do subset analyses and there may be some benefit for adding radiation to the stage threes. But again, it’s exploratory, it’s hypothesis-generating. The results don’t surprise me. I mean, it took so long to do — maybe because it wasn’t done outside of the NCI — and it shows; the study design doesn’t have any targeted therapy in it. It was good to present these data to get the final OS and everything, but nothing really surprising.

Matulonis: Yeah. Yeah. Katie?

Moore: Yeah, I have really nothing to add. I think the best thing about this study, other than it was incredibly well done and Dr. Matei should be congratulated along with the NCI, but really these are important to read out just so we have benchmarks. So, when we design the next study, we know what the benchmark is for the control arm. So, this really gives us probably the most modern-era look with modern-era radiation — and, of course, chemotherapy hasn’t changed, it’s just carbo-paclitaxel — what OS looks like in this high-risk adjuvant population. So, that’s the statistics that’s going to be my control arm to improve on.

So, it’s important data to get out there and I was pleased to see it, but I don’t think there was anything that I want — I’m not designing the next trial based on this <laughter>.

Matulonis: Yeah. Right. Got it. But I think it also puts in the question, and our group has had this discussion, around when to use radiotherapy. Obviously, the two arms were negative in terms of OS there’s really no difference. But again, bringing in RUBY and GY018, which really didn’t tell us when we should be using radiation therapy or what’s the safety of using IO with radiation therapy, but are there situations where patients who are newly diagnosed — obviously, recurrence is a little bit different story — but bulky nodes or extensive nodal disease, where you do use radiation therapy, or is that going to be really kind of sidelined at this point? Because I definitely hear different institutions doing different things around the use of radiation therapy. Krish, do you want to start?

Tewari: Yeah, it’s a great question. Bulky unresectable nodes, I wouldn’t radiate them. I’m going to hope that adding IO to the chemo is going to help those patients. But where I’ve used radiation is, before we had any of these new targeted therapies, is I had positive nodes that I removed that were found to be positive and I would give them chemotherapy and radiate the nodal beds once the disease has been removed. I don’t know if that’s necessary anymore. And we just don’t know.

Certainly, once the labels come out in whatever populations we can treat with chemo plus IO, if they have a complete response or if they had a complete surgical response and then we treat them with adjuvant chemo plus IO and nothing crops up for some time, I’m probably not going to add radiation to the mix. We used to do this thing — we’d sandwich a few cycles of chemo, give radiation, give some more chemo — that may go away. That may go away.

Matulonis: Yeah, Katie?

Moore: I really feel like a lot of this is institutionally driven. In our institution I have fantastic radiation oncologists, but they’re not pushing us to give everyone whole pelvic radiation per this regimen. And I don’t get to see these patients as much anymore. These are more the patients my partner sees. But I see them using vaginal cuff brachytherapy. When they’ve resected someone that’s got a big cervix and then they put them right on chemo. So radiation even for bulky nodes, has fallen off at our institution. It’s primarily a chemotherapy- and targeted-therapy world.

Matulonis: Yeah, it’s interesting. Yeah, I think it really is institutionally driven. But these studies don’t help us with that. So, we’re going to have to sort of figure this out.

All right. I want to thank you both. A real pleasure, honor to be with you and to talk about SGO 2023 and look forward to upcoming ASCO.

Tewari: Fantastic. Thanks so much.

Moore: Thanks for having me.

Watch episode one: A Deep Dive Into Two Randomized Trials in Endometrial Cancer

Watch episode two: Choosing a Treatment Regimen for Your Endometrial Cancer Patients

Watch episode three: Sobering OS Data With Maintenance Niraparib in Recurrent Ovarian Cancer

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