Advanced Endometrial Cancer - Episode 4

GOG 0209 Study in Advanced Endometrial Cancer

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Bradley J. Monk, MD, FACS, FACOG: Krish, I’m going to come back to you. You said, “Let’s treat the patient.” What are some of the challenges you have in treating in an adjuvant setting, so after hysterectomy? Or do you have it all worked out in your mind? In other words, who should get adjuvant treatment? I’m not going to ask you to get into the studies. We’re going to that next. But just summarize, in a statement or 2, who needs adjuvant treatment for endometrial cancer.

Krishnansu S. Tewari, MD: You’ve got a well surgically staged patient; you can use the GOG-99 criteria to determine if they adjuvant radiotherapy. If you’ve got a surgically staged patient with a positive node, they need chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: I love it. See, we’re getting simple here, guys. If you have a deeply invasive or a grade 3 tumor or cervical extension, you give them pelvic radiation. In other words, it’s a chemotherapy world. I love it. Let’s talk now, Katie Moore, about what the standard chemotherapy is, published this year by our friend David Miller. Tell us about GOG-0209.

Kathleen N. Moore, MD: Right. We’ve been waiting for this publication. We saw the abstract for it in 2011 or 2012, and we’ve been waiting for this paper for a long time. The reason it took so long is actually not laziness. It’s just that the patients did really well. It took a long time to reach the end points. This is how long it takes to do trials. This was a really important study. It’s very different from preceding studies that had set the standard of care in the past, which had been Adriamycin and cisplatin, after a series of studies done in stage IV recurrent disease. GOG-0209, led by Dr David Miller, had those patients, but also had adjuvant patients. You just referred to that, Dr Monk. For these patients who are fully staged and apparently stage I, then you find a node. Now we call stage IIIC1 or IIIC2. They were all included as well. It’s a very different prognostic group of patients included in GOG-0209. It took what was the community standard at that time—paclitaxel and carboplatin, which is identical to what we do in ovarian cancer—and compared it with what had been the preceding winning arm in endometrial cancer, which was a triplet: paclitaxel, Adriamycin, and cisplatin, which requires GCSF support to give. It was a noninferiority study. No one thought it was going to be better, but it is as good and certainly far more convenient and less toxic. GOG-0209 showed us that, indeed, it is noninferior. It’s pretty much identical if you look at the overall end point, which was overall survival. Why it took so long? If you look at overall survival, it’s completely noninferior and almost identical. If you look at the paper, the curves basically sit on one another with medians of 37 and 41 months.

Probably the most interesting part—and really why I wanted to see the paper—is that they did break out the adjuvant group from the measurable disease group. Because I’m interested to see what that looks like in a nonbiologic therapy era. We’re going to talk about the biologic therapies coming up. But if you use just chemotherapy, what do you get? These are benchmarking data. If you look at the measurable disease—identical, 20 to 22 months median—that’s better than what we’ve seen in the past.

Bradley J. Monk, MD, FACS, FACOG: PFS or OS [overall survival]?

Kathleen N. Moore, MD: That is…

Bradley J. Monk, MD, FACS, FACOG: For 22 months?

Kathleen N. Moore, MD: That is PFS.

Kathleen N. Moore, MD: Yeah.

Bradley J. Monk, MD, FACS, FACOG: Long time.

Kathleen N. Moore, MD: Long time. That’s measurable disease.

Bradley J. Monk, MD, FACS, FACOG: Right.

Kathleen N. Moore, MD: PFS for the nonmeasurable—basically, these patients are cured. They just never reached it. We had like 112 months vs nonreached. They had a lot of patients in this group cured with chemotherapy. It gives us standard toxicity comparisons that I don’t think we need to belabor here. We all know that paclitaxel-carboplatin is well tolerated and certainly better tolerated than the triplet. I believe we all moved to this many years ago. But if there was any question of what the superior regimen or backbone should be, it should be well established now that it’s paclitaxel-carboplatin.

Bradley J. Monk, MD, FACS, FACOG: Very succinct. Thank you. Global standards. Dave, I’m going to ask you a tough question. I think I know the answer. I’m not sure. Are the endometroid tumors or the serous tumors more chemotherapy sensitive? Or you don’t know? Or they’re the same? Does it matter? Are the endometroid tumors less sensitive or more sensitive than the serous tumors?

David M. O’Malley, MD: We’re seeing across time that both of them respond to chemotherapy almost equally. As we look at some of the other challenges with the poor prognosis of serous cancers, they are usually explained by other risk factors. As we look at these trials, we see that both types respond to chemotherapy. Maybe it’s slightly more in serous, but it’s not enough to deny anybody chemotherapy based on their histology.

Bradley J. Monk, MD, FACS, FACOG: I love that answer. Brian?

Brian M. Slomovitz, MD: I like speaking after Dave because I get to look smarter. I agree. The only other thing is that the chemotherapy is the same for grade 3 endometrioid cancers. Grade 1 and 2 are more hormonally responsive. Fewer cells are in the cell cycle. The low-grade endometrioid cancer doesn’t respond as well to chemotherapy as high grade. But high-grade endometrioid, serous, and carcinosarcomas are in the same category.

The PFS for those patients with tumor is worth repeating. It’s measurable disease. What’s the PFS from GOG-0209?

Kathleen N. Moore, MD: 20 to 22 months.

Bradley J. Monk, MD, FACS, FACOG: You guys have done such a great job teaching the world that these cervical and endometrial cancers are chemotherapy sensitive. That’s what I was trying to get you to say, Dave. And that’s probably the right answer. With PFS of over 20 months, they both work.

Transcript Edited for Clarity