GOG-258 and PORTEC-3 Studies in Endometrial Cancer

Bradley J. Monk, MD, FACS, FACOG: Brian, I think this study GOG-258, which was first authored by Daniela Matei, MD, published in The New England Journal of Medicine, of both—we’ve been talking radiation versus chemotherapy—but this is both versus chemotherapy. I think the reason it was published in The New England Journal of Medicine is because it did not show that chemotherapy and radiation was better than chemotherapy. It was published to encourage people to stop giving chemotherapy and radiation. But I don’t know. Brian, tell me what you think about GOG-258 and what’s the real interpretation.

Brian M. Slomovitz, MD: To Katie’s point, GOG-258’s really a group of high-risk individuals. In GOG-249, there was no difference because if you’re not going to recur, it doesn’t matter what you give. But GOG-258 was truly high-risk individuals. They gave the best chemotherapy that we thought at the time. The study made an assumption going in that Taxol/carbo [paclitaxel and carboplatin] was going to be the best chemotherapy, because it was prior to the publication of GOG-209. They compared it to a regimen of a heavy dose of cisplatin, 50 mg with radiation, followed by 4 doses of carboplatin and paclitaxel.

What they found is the addition of the radiation for the entire group did not have a superior outcome to those patients who just got chemotherapy alone. Now there’s a subgroup analysis in those patients that had a target to radiate. Meaning, if they didn’t give whole pelvic, if it was more target directed, those patients may benefit from some radiotherapy. But in general, the typical advanced-stage patient, node positive, node was resected, endometrial cancer, the study is definitive evidence that says chemotherapy alone is enough. We don’t need to radiate those patients.

Bradley J. Monk, MD, FACS, FACOG: Thanks, Brian, that’s very succinct. I keep coming back to you, Krish. In your practice, when do you use chemotherapy and radiation in endometrial cancer?

Krishnansu S. Tewari, MD: I don’t.

Bradley J. Monk, MD, FACS, FACOG: All right. Well, that’s pretty simple.

Krishnansu S. Tewari, MD: I told you, if they’ve got advanced disease then chemotherapy. If they’ve got high-risk, early stage disease, it’s adjuvant radiotherapy.

Bradley J. Monk, MD, FACS, FACOG: I love the practicality and quite frankly, I agree with you. Dave, there was this paper called PORTEC-3, which I don’t understand. I’m not even going to start. I’m turning it over to one of my smartest friends. Tell me what this trial is. It’s gotten a lot of attention. Put this PORTEC-3 into perspective.

David M. O’Malley MD: Well, PORTEC-3 was a European trial. It’s actually 2 publications. The first publication looked at the clinical outcomes in a very—you used the word heterogenous group earlier in this conversation. This was a very mixed bag. So stage I, grade 3 with deep invasion, or lymph vascularization, or both. As well as stage II, stage III or any patients with stage I to III serous or clear cell endometrial cancer. So, a very mixed group of patients. Basically, what they compared was whole pelvic radiation versus chemotherapy plus whole pelvic radiation. We were having a conversation….

Bradley J. Monk, MD, FACS, FACOG: Wait, Dr Tewari said if I got a positive node, the control arm is chemotherapy.

David M. O’Malley MD: Well, you have a very strong argument with regard to data that we’ve already reviewed, that the control arm should have been chemotherapy. In some of these patients, the control arm should have been nothing or vaginal cuff brachytherapy to support the previous PORTEC trials. So when we look at this, we call into question, but when you bring in stage III, it’s a diverse group of patients, to say the least. But interestingly, they showed improvements with the chemotherapy. As we’ve already talked about, that should have been no surprise. To the radiation therapist on the clinical trial, I think it was.

So 5-year overall survival benefits by about 7%. The hazard ratio was about 0.7. Failure-free survival, the same thing, about a 6% improvement. When we look at those groups of patients, the addition of chemotherapy to radiation showed improvement in this entire population. We can talk more about the population, the molecular changes, but I’ll stop there.

Bradley J. Monk, MD, FACS, FACOG: I think I’m going to keep moving. To your point, and thank you for being so good natured, it shows that chemotherapy works when used in the adjuvant setting, which is what Dr Tewari said. He said it when he subanalyzed GOG-122 and he practices it, as all of you do, and Dr Slomovitz says that the addition of radiation doesn’t do much to it. I think we’ve set the standard.

Transcript Edited for Clarity