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HIPEC in Advanced Ovarian Cancer

Panelists: Bradley J. Monk, MD, FACS, FACOG, University of Arizona, Creighton University, & Arizona Oncology Practice of US Oncology; Ursula Matulonis, MD, Dana-Farber Cancer Institute; David OMalley, MD, The Ohio State University; Matthew Powell, MD, Washington University; Shannon N. Westin, MD, MPH, MD Anderson Cancer Center
Published: Thursday, Apr 26, 2018



Transcript: 

Bradley J. Monk, MD, FACS, FACOG: A recently published manuscript suggested that maybe, at the time of the second surgery, after neoadjuvant chemotherapy, we should use heated intraperitoneal chemotherapy (HIPEC). Can you tell us about that study, Shannon?

Shannon N. Westin, MD, MPH: Sure. You’re talking about the van Driel study, which was just published in the New England Journal of Medicine. This is an interesting study that looked at patients who had been deemed as unresectable, who were going to get neoadjuvant chemotherapy, and randomized them. If the patient had a response, or at least stable disease after 3 cycles of standard Taxol and carboplatin, they were randomized to either receive heated intraperitoneal chemotherapy with cisplatin, or regular surgery followed by 3 additional cycles.

All patients received another 3 cycles of intravenous therapy after the completion of their surgery. About 245 patients were randomized. And what they found was improved progression-free survival—about 4 months improved progression-free survival in the patients who got HIPEC at the time of their debulking surgery—as well as improved overall survival—about 11 months improvement in overall survival for 45 months overall survival in those patients who got HIPEC.

However, there were some setbacks. Although they said the toxicity and the complications were about the same, when you looked at and dug into some of the surgical outcomes, almost 70%, or I think 72% of the patients had a colostomy or an ileostomy.

Bradley J. Monk, MD, FACS, FACOG: In both groups?

Shannon N. Westin, MD, MPH: In the group who got HIPEC.

Bradley J. Monk, MD, FACS, FACOG: It’s weird, huh?

Shannon N. Westin, MD, MPH: Yes, it’s weird. It wasn’t something that was mandated, and they don’t really have a good explanation for it. They thought it might just be surgeon’s choice. “Hey, I gave this patient HIPEC. I did a bowel resection. I’m going to go ahead and bring up an ileostomy for protection.” But, they don’t really know why that was. Certainly, we’re talking about neoadjuvant therapy and reducing the need for bowel resections, ileostomies, and colostomies, and now we’re adding HIPEC and are potentially increasing dosage. I think it’s also important to note that when you look, the progression-free survival of 14 months….

Bradley J. Monk, MD, FACS, FACOG: Ten versus 14—4 months progression-free survival.

Shannon N. Westin, MD, MPH: Yes, 4 months progression-free survival. I know we don’t do cross-trial comparisons, but when we look at the 14 months, that’s not all that different from some of our studies that looked at suboptimal patient populations with dose-dense chemotherapy or the addition of bevacizumab.

Bradley J. Monk, MD, FACS, FACOG: What you said is that there’s no way to do a blinded surgical study? And once you begin to do a blinded surgical or intraperitoneal study like this, systematic biases are introduced?

Shannon N. Westin, MD, MPH: Absolutely

David O’Malley, MD: Well, you also have a European trial here, with a different postoperative management strategy. Their average length of stay was 8 to 9 days in both groups. Our average length of stay after a surgery like this would be 3 or 4 days. So, to say there’s no difference in the surgical complications, in those who have done HIPEC, clearly the bowel dysfunction and the prolonged postoperative ileus is much higher in the HIPEC arm, which is not identified in this case because they’re in the hospital for so long.

Bradley J. Monk, MD, FACS, FACOG: Yes, it’s controversial. This particular study, at the ASCO Annual Meeting in 2017, did not even get an oral or poster discussion. It was a poster. But, the New England Journal of Medicine thought it was publication worthy. Clearly, that illustrates the controversy. In Boston or St. Louis, are you guys doing HIPEC?

Ursula Matulonis, MD: Our surgeons are starting to think about doing this. Again, it’s going to be for a highly selected patient population. I think the results are intriguing. At least one of our surgeons is starting to select patients to do it.

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

Matthew Powell, MD: We have had a long-term program, mostly in our mucinous tumors. It’s taken a while to establish a standard within that field of peritoneal mucinous-based tumors. The controversy with this trial is that the side effects in the manuscript are surprisingly low. The challenge with this ostomy issue is a little tricky because the patients who had bowel resection of some type that protect the ostomy was much more. So, a lot of patients didn’t need bowel resection as part of their debulking surgery. They’re not included in that 72% number. So, don’t think that 72% of all patients who had HIPEC had an ostomy—that’s actually not the case. It’s much lower than that.

The issue with us developing a program—patients are asking for it, we’re thinking about it, and we’re in the same boat. We’re not quite there, as far as doing it routinely. We still think these patients probably should be on a research protocol, at least for capturing these side effects. Are we going to do as well in a lower-volume center versus an area that’s been doing it for 10 years? I think these are very important things to help protect our patients.

Bradley J. Monk, MD, FACS, FACOG: We looked at it in Phoenix. We actually looked at it in journal club, which was fun. We decided not to do it. We think that it’s still investigational. We think you have to look at the totality of the data. And, you probably have heard me say that it takes 2 trials to convince anyone of anything. I’ll say that again, as we talk about other modalities that are not substantiated by 2 trials.

Ursula Matulonis, MD: There have been several trials on intraperitoneal chemotherapy. Many of the trials have been positive for overall survival. So, in this trial, it’s not surprising that there was an overall survival improvement, especially with the use of cisplatin chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: It was 7 cycles though, versus 6.

Ursula Matulonis, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: So, the only trial to isolate the effect in question—in GOG 252, intraperitoneal chemotherapy, as you know, was negative. Every other trial like this one introduces other factors, differences in surgery, differences in dose, and differences in schedules. So, this controversy will continue.

Matthew Powell, MD: But Brad, 5 versus 10? We had 6 versus 12. I don’t think you do 6 versus 7?

David O’Malley, MD: But Matt, from my reading of this paper and based on our own journal club discussion at Ohio State, we also don’t think this is ready for prime time. This needs to be done in prospective evaluation. We have to do it in clinical trial. That’s going to take away from the other 7 or 8 very exciting clinical trials that we have.

Bradley J. Monk, MD, FACS, FACOG: With checkpoint inhibitors and PARP inhibitors.

Shannon N. Westin, MD, MPH: In combination.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: A recently published manuscript suggested that maybe, at the time of the second surgery, after neoadjuvant chemotherapy, we should use heated intraperitoneal chemotherapy (HIPEC). Can you tell us about that study, Shannon?

Shannon N. Westin, MD, MPH: Sure. You’re talking about the van Driel study, which was just published in the New England Journal of Medicine. This is an interesting study that looked at patients who had been deemed as unresectable, who were going to get neoadjuvant chemotherapy, and randomized them. If the patient had a response, or at least stable disease after 3 cycles of standard Taxol and carboplatin, they were randomized to either receive heated intraperitoneal chemotherapy with cisplatin, or regular surgery followed by 3 additional cycles.

All patients received another 3 cycles of intravenous therapy after the completion of their surgery. About 245 patients were randomized. And what they found was improved progression-free survival—about 4 months improved progression-free survival in the patients who got HIPEC at the time of their debulking surgery—as well as improved overall survival—about 11 months improvement in overall survival for 45 months overall survival in those patients who got HIPEC.

However, there were some setbacks. Although they said the toxicity and the complications were about the same, when you looked at and dug into some of the surgical outcomes, almost 70%, or I think 72% of the patients had a colostomy or an ileostomy.

Bradley J. Monk, MD, FACS, FACOG: In both groups?

Shannon N. Westin, MD, MPH: In the group who got HIPEC.

Bradley J. Monk, MD, FACS, FACOG: It’s weird, huh?

Shannon N. Westin, MD, MPH: Yes, it’s weird. It wasn’t something that was mandated, and they don’t really have a good explanation for it. They thought it might just be surgeon’s choice. “Hey, I gave this patient HIPEC. I did a bowel resection. I’m going to go ahead and bring up an ileostomy for protection.” But, they don’t really know why that was. Certainly, we’re talking about neoadjuvant therapy and reducing the need for bowel resections, ileostomies, and colostomies, and now we’re adding HIPEC and are potentially increasing dosage. I think it’s also important to note that when you look, the progression-free survival of 14 months….

Bradley J. Monk, MD, FACS, FACOG: Ten versus 14—4 months progression-free survival.

Shannon N. Westin, MD, MPH: Yes, 4 months progression-free survival. I know we don’t do cross-trial comparisons, but when we look at the 14 months, that’s not all that different from some of our studies that looked at suboptimal patient populations with dose-dense chemotherapy or the addition of bevacizumab.

Bradley J. Monk, MD, FACS, FACOG: What you said is that there’s no way to do a blinded surgical study? And once you begin to do a blinded surgical or intraperitoneal study like this, systematic biases are introduced?

Shannon N. Westin, MD, MPH: Absolutely

David O’Malley, MD: Well, you also have a European trial here, with a different postoperative management strategy. Their average length of stay was 8 to 9 days in both groups. Our average length of stay after a surgery like this would be 3 or 4 days. So, to say there’s no difference in the surgical complications, in those who have done HIPEC, clearly the bowel dysfunction and the prolonged postoperative ileus is much higher in the HIPEC arm, which is not identified in this case because they’re in the hospital for so long.

Bradley J. Monk, MD, FACS, FACOG: Yes, it’s controversial. This particular study, at the ASCO Annual Meeting in 2017, did not even get an oral or poster discussion. It was a poster. But, the New England Journal of Medicine thought it was publication worthy. Clearly, that illustrates the controversy. In Boston or St. Louis, are you guys doing HIPEC?

Ursula Matulonis, MD: Our surgeons are starting to think about doing this. Again, it’s going to be for a highly selected patient population. I think the results are intriguing. At least one of our surgeons is starting to select patients to do it.

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

Matthew Powell, MD: We have had a long-term program, mostly in our mucinous tumors. It’s taken a while to establish a standard within that field of peritoneal mucinous-based tumors. The controversy with this trial is that the side effects in the manuscript are surprisingly low. The challenge with this ostomy issue is a little tricky because the patients who had bowel resection of some type that protect the ostomy was much more. So, a lot of patients didn’t need bowel resection as part of their debulking surgery. They’re not included in that 72% number. So, don’t think that 72% of all patients who had HIPEC had an ostomy—that’s actually not the case. It’s much lower than that.

The issue with us developing a program—patients are asking for it, we’re thinking about it, and we’re in the same boat. We’re not quite there, as far as doing it routinely. We still think these patients probably should be on a research protocol, at least for capturing these side effects. Are we going to do as well in a lower-volume center versus an area that’s been doing it for 10 years? I think these are very important things to help protect our patients.

Bradley J. Monk, MD, FACS, FACOG: We looked at it in Phoenix. We actually looked at it in journal club, which was fun. We decided not to do it. We think that it’s still investigational. We think you have to look at the totality of the data. And, you probably have heard me say that it takes 2 trials to convince anyone of anything. I’ll say that again, as we talk about other modalities that are not substantiated by 2 trials.

Ursula Matulonis, MD: There have been several trials on intraperitoneal chemotherapy. Many of the trials have been positive for overall survival. So, in this trial, it’s not surprising that there was an overall survival improvement, especially with the use of cisplatin chemotherapy.

Bradley J. Monk, MD, FACS, FACOG: It was 7 cycles though, versus 6.

Ursula Matulonis, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: So, the only trial to isolate the effect in question—in GOG 252, intraperitoneal chemotherapy, as you know, was negative. Every other trial like this one introduces other factors, differences in surgery, differences in dose, and differences in schedules. So, this controversy will continue.

Matthew Powell, MD: But Brad, 5 versus 10? We had 6 versus 12. I don’t think you do 6 versus 7?

David O’Malley, MD: But Matt, from my reading of this paper and based on our own journal club discussion at Ohio State, we also don’t think this is ready for prime time. This needs to be done in prospective evaluation. We have to do it in clinical trial. That’s going to take away from the other 7 or 8 very exciting clinical trials that we have.

Bradley J. Monk, MD, FACS, FACOG: With checkpoint inhibitors and PARP inhibitors.

Shannon N. Westin, MD, MPH: In combination.

Transcript Edited for Clarity 
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