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Neoadjuvant Therapy in Advanced Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, Arizona Oncology Practice of US Oncology; Oliver Dorigo, MD, PhD, Stanford University Medical Center; Thomas Herzog, MD, University of Cincinnati Cancer Institute; Kathleen Moore, MD, Stephenson Cancer Center; Leslie M. Randall, MD, MAS, University of California, Irvine
Published: Thursday, Aug 16, 2018



Transcript: 

Oliver Dorigo, MD, PhD: I think that the neoadjuvant chemotherapy principle is being adopted in the United States. Nationwide, about 50% of patients undergo neoadjuvant chemotherapy. It’s similar in my division. I think that the Europeans are ahead of us. The percentages are even higher in some countries. We might, and I wonder what you guys think, at some point say that all newly diagnosed advanced ovarian cancer patients should have neoadjuvant chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: We’ll get to that question because in secondary cytoreduction, the answer is that surgery probably doesn’t help. We’ll get to that. But in your world, what percentage of patients, after going through these complicated algorithms, get neoadjuvant chemotherapy?

Kathleen Moore, MD: Definitely more than in the past, but I would say we are still probably treating 60% to 70% with primary cytoreduction.

Bradley J. Monk, MD, FACS, FACOG: Really?

Leslie M. Randall, MD, MAS: Yes.

Kathleen Moore, MD: Dr Dorigo may be right, or I may be right. I really believe in primary cytoreduction. One of these 2 groups is going to have a come-to-Jesus moment when the TRUST study is finally done. Hopefully that study is going to answer this question.

Bradley J. Monk, MD, FACS, FACOG: Tell us what that study is.

Kathleen Moore, MD: The TRUST study is mainly being run in Europe. There are a few United States sites, I believe. It’s randomizing consecutive patients to either primary cytoreduction or neoadjuvant chemotherapy.  You have to agree to offer this study to consecutive patients. The patients can opt out. You have to agree that you’re not going to select. You’re not going to cherry-pick. No. 2, the only way you could enter the study is if you had proven that you could operate, and that you could get to R0.

Bradley J. Monk, MD, FACS, FACOG: What do you mean? There are surgeons that can’t operate?

Kathleen Moore, MD: There are surgeons that aren’t going to get someone to R0.

Bradley J. Monk, MD, FACS, FACOG: Aggressive … You mean they have better judgment?

Kathleen Moore, MD: I think that may be true, or not.

Leslie M. Randall, MD, MAS: It depends on the situation.

Kathleen Moore, MD: I think it depends on the situation. We don’t like to say that out loud, but if you have porta hepatis disease, can you get that out? Sure. You can if you have a hepatobiliary surgeon helping you in the operating room. I think there are different radicalities, different thresholds, that people have. They had to prove that they had achieved a certain level of R0 resection to even participate on the trial.

Bradley J. Monk, MD, FACS, FACOG: Tom, you practice in a metropolitan area. What do you think is an appropriate rate of neoadjuvant chemotherapy?

Thomas Herzog, MD: I have a pattern that’s probably very close to yours right now. I’d say that 60% of our patients are probably getting primary cytoreduction, and about 40% are getting neoadjuvant therapy. Five years ago, I was probably giving neoadjuvant therapy in 10% of patients. Now I’m at 40%. I’ve moved a long way toward that. The SGO issued a nice statement about this. The other thing that I would say is that with the concern for neoadjuvant therapy, a couple of things are interesting, right? You decrease the death rate, which is low, overall. You decrease surgical mortality. You decrease surgical morbidity. You cut it in half. You more than double the optimal cytoreductive rate, and you more than double the R0 rate, getting to no gross disease.

Bradley J. Monk, MD, FACS, FACOG: That’s why we do it.

Thomas Herzog, MD: Which should convert to a better outcome, but it has not.

Bradley J. Monk, MD, FACS, FACOG: It does convert to a better outcome in select patients. It’s all about patient selection. In all comers, no?

Thomas Herzog, MD: It doesn’t in terms of survival. The survival is the same, and that is the concerning part of this discussion. You look at the survival from both CHORUS and from EORTC. The EORTC study had particularly large tumors—greater than 10 cm. CHORUS had more of a normal real-world data set. In both of these trials, the median survivals are approximately 29, 30 months. If you look at contemporary series from major centers with aggressive cytoreductive programs, those median survivals are 45 to 50 months. That makes it concerning. Yes, there’s cherry-picking going on, etc, etcetera. That’s why people are concerned.

Bradley J. Monk, MD, FACS, FACOG: It’s the hardest decision we make.

Thomas Herzog, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: That’s why we’re having such a spirited discussion. The criteria are unclear. The last thing you want to do is have the patient get seen by a medical oncologist and start chemotherapy without having a formal consultation with the surgeon. I think that’s really the take-home message.

Thomas Herzog, MD: It’s an important part of this discussion.

Oliver Dorigo, MD, PhD: And unfortunately, that happens way too often.

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

Oliver Dorigo, MD, PhD: That’s a message that we have to get out there.

Bradley J. Monk, MD, FACS, FACOG: Thank you for that.

Oliver Dorigo, MD, PhD: In that context, Dr. Fagotti, out of Italy, presented the SCORPION trial, which is actually designed as a superiority study. The hypothesis is that neoadjuvant chemotherapy does better, just like you suggested. We’ll see what the study shows. Based on the abstract, there doesn’t seem to be too much of a difference.

Bradley J. Monk, MD, FACS, FACOG: That’s right.

Transcript Edited for Clarity 

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Transcript: 

Oliver Dorigo, MD, PhD: I think that the neoadjuvant chemotherapy principle is being adopted in the United States. Nationwide, about 50% of patients undergo neoadjuvant chemotherapy. It’s similar in my division. I think that the Europeans are ahead of us. The percentages are even higher in some countries. We might, and I wonder what you guys think, at some point say that all newly diagnosed advanced ovarian cancer patients should have neoadjuvant chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: We’ll get to that question because in secondary cytoreduction, the answer is that surgery probably doesn’t help. We’ll get to that. But in your world, what percentage of patients, after going through these complicated algorithms, get neoadjuvant chemotherapy?

Kathleen Moore, MD: Definitely more than in the past, but I would say we are still probably treating 60% to 70% with primary cytoreduction.

Bradley J. Monk, MD, FACS, FACOG: Really?

Leslie M. Randall, MD, MAS: Yes.

Kathleen Moore, MD: Dr Dorigo may be right, or I may be right. I really believe in primary cytoreduction. One of these 2 groups is going to have a come-to-Jesus moment when the TRUST study is finally done. Hopefully that study is going to answer this question.

Bradley J. Monk, MD, FACS, FACOG: Tell us what that study is.

Kathleen Moore, MD: The TRUST study is mainly being run in Europe. There are a few United States sites, I believe. It’s randomizing consecutive patients to either primary cytoreduction or neoadjuvant chemotherapy.  You have to agree to offer this study to consecutive patients. The patients can opt out. You have to agree that you’re not going to select. You’re not going to cherry-pick. No. 2, the only way you could enter the study is if you had proven that you could operate, and that you could get to R0.

Bradley J. Monk, MD, FACS, FACOG: What do you mean? There are surgeons that can’t operate?

Kathleen Moore, MD: There are surgeons that aren’t going to get someone to R0.

Bradley J. Monk, MD, FACS, FACOG: Aggressive … You mean they have better judgment?

Kathleen Moore, MD: I think that may be true, or not.

Leslie M. Randall, MD, MAS: It depends on the situation.

Kathleen Moore, MD: I think it depends on the situation. We don’t like to say that out loud, but if you have porta hepatis disease, can you get that out? Sure. You can if you have a hepatobiliary surgeon helping you in the operating room. I think there are different radicalities, different thresholds, that people have. They had to prove that they had achieved a certain level of R0 resection to even participate on the trial.

Bradley J. Monk, MD, FACS, FACOG: Tom, you practice in a metropolitan area. What do you think is an appropriate rate of neoadjuvant chemotherapy?

Thomas Herzog, MD: I have a pattern that’s probably very close to yours right now. I’d say that 60% of our patients are probably getting primary cytoreduction, and about 40% are getting neoadjuvant therapy. Five years ago, I was probably giving neoadjuvant therapy in 10% of patients. Now I’m at 40%. I’ve moved a long way toward that. The SGO issued a nice statement about this. The other thing that I would say is that with the concern for neoadjuvant therapy, a couple of things are interesting, right? You decrease the death rate, which is low, overall. You decrease surgical mortality. You decrease surgical morbidity. You cut it in half. You more than double the optimal cytoreductive rate, and you more than double the R0 rate, getting to no gross disease.

Bradley J. Monk, MD, FACS, FACOG: That’s why we do it.

Thomas Herzog, MD: Which should convert to a better outcome, but it has not.

Bradley J. Monk, MD, FACS, FACOG: It does convert to a better outcome in select patients. It’s all about patient selection. In all comers, no?

Thomas Herzog, MD: It doesn’t in terms of survival. The survival is the same, and that is the concerning part of this discussion. You look at the survival from both CHORUS and from EORTC. The EORTC study had particularly large tumors—greater than 10 cm. CHORUS had more of a normal real-world data set. In both of these trials, the median survivals are approximately 29, 30 months. If you look at contemporary series from major centers with aggressive cytoreductive programs, those median survivals are 45 to 50 months. That makes it concerning. Yes, there’s cherry-picking going on, etc, etcetera. That’s why people are concerned.

Bradley J. Monk, MD, FACS, FACOG: It’s the hardest decision we make.

Thomas Herzog, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: That’s why we’re having such a spirited discussion. The criteria are unclear. The last thing you want to do is have the patient get seen by a medical oncologist and start chemotherapy without having a formal consultation with the surgeon. I think that’s really the take-home message.

Thomas Herzog, MD: It’s an important part of this discussion.

Oliver Dorigo, MD, PhD: And unfortunately, that happens way too often.

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

Oliver Dorigo, MD, PhD: That’s a message that we have to get out there.

Bradley J. Monk, MD, FACS, FACOG: Thank you for that.

Oliver Dorigo, MD, PhD: In that context, Dr. Fagotti, out of Italy, presented the SCORPION trial, which is actually designed as a superiority study. The hypothesis is that neoadjuvant chemotherapy does better, just like you suggested. We’ll see what the study shows. Based on the abstract, there doesn’t seem to be too much of a difference.

Bradley J. Monk, MD, FACS, FACOG: That’s right.

Transcript Edited for Clarity 
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