GOG-249 Study in Early-Stage Endometrial Cancer

Bradley J. Monk, MD, FACS, FACOG: Krish, you had mentioned this high-risk, high-intermediate risk GOG-99 group, deeply invasive, maybe limited to the uterus, serous tumors, cervical involvement. You had participated and been an advocate for this study led by Scott McMeekin, MD, FACOG, FACS until his untimely death, GOG-249. Tell us what the intention was of GOG-249 trying to beat pelvic radiation as the standard in that high-risk limited to the uterus subgroup.

Krishnansu S. Tewari, MD: It was taking a riff on what was done in cervical cancer and trying to see if chemotherapy could make the radiation work a little better and also eradicate distant metastases. There was a lot of thought that even serous cancers are going to respond better to this treatment approach because of the chemotherapy. But it really didn’t pan out. They had a good percentage of serous cancers in the study. But right now, if I have a high-risk, early stage endometrial cancer, I’m treating them with adjuvant radiotherapy.

Bradley J. Monk, MD, FACS, FACOG: That would be the ASTRO [American Society for Radiation Oncology] guidelines. Katie Moore, so what it was is pelvic radiation, limited to the uterus, but still serious cancer, versus vaginal brachytherapy in 3 doses of chemotherapy, trying, as you said Krish, to get a systemic effect. Is the reason that that study did not show superiority of vaginal brachytherapy in chemotherapy because we only gave 3 cycles? What do you think?

Kathleen N. Moore, MD: No, I don’t think so. I think we have a lot to learn from this study. I’m hopeful we’ll do some subgroup analyses from it. But I think the same problem plagued this study as has plagued other stage I endometrial cancer studies, is that we’re just not great at predicting that group of patients who are really high risk. The GOG-99 criteria, I respect them and the time, but I think they’re not the criteria that really identify the patients who need therapy. It’s probably all 3 risk factors. If you look at the breakdown, and I think we’ll see this from the GOG-249 exploratory. But if you look at those who have deep invasion, high grade and are of older age, all 3, that may be the group who benefits from chemotherapy. They’re all clinical factors. We haven’t incorporated the pathologic factors we’ve talked about, as well, to really identify that 15% who need more help. Then the rest probably don’t need it.

Bradley J. Monk, MD, FACS, FACOG: Yes. Krish, you wrote a very nice subset paper of GOG-122, chemotherapy versus radiation in node-positive disease. You said, “Well, what if there’s just 1 node? Maybe radiation is good enough.” But your findings suggested even where there’s 1 node, that 3C1 tumor, that chemotherapy is better, right?

Krishnansu S. Tewari, MD: That’s right. It’s exploratory. But you’d think that a single positive node, radiation should be just as effective. But we found that if it was a single positive node, chemotherapy is still better. We also found, even if there was just isolated cervical involvement, chemotherapy is better.

Bradley J. Monk, MD, FACS, FACOG: Again, to Brian and Dave’s point, chemotherapy works. It works regardless of the cell type as Dave was saying.

Transcript Edited for Clarity