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Incorporating Bevacizumab into First-Line Practice for EOC

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: We have 3 challenges to filing, with GOG-0218. One is the NCCN. The second, which we’ll talk about it in a minute, is how bevacizumab now works in neoadjuvant therapy, because that wasn’t included. The third is, is this really just a high-risk opportunity—patients with stage 4, large volume residual disease—because that might be where the biggest benefit is, at least in ICON7? Is it going to change your practice, to get it FDA approved?

David O’Malley, MD: You know, it will change practice. There are a lot of regional differences between the approval of bevacizumab in the upfront setting. And so, we have a lot of trouble getting approval for bevacizumab in the upfront setting.

Bradley J. Monk, MD, FACS, FACOG: Payment, you mean?

David O’Malley, MD: Correct. That’s a good point—payment for these drugs. In those patients who I want to give bevacizumab, and you already identified those high-risk patients—large ascites, large volume disease, extra-abdominal disease—I will utilize bevacizumab. In the past, I wasn’t able to.

Bradley J. Monk, MD, FACS, FACOG: That’s interesting. How about you guys? Is it going to change your uptake?

Matthew Powell, MD: Yes. And the other thing I’m excited about is, we saw the translational science in GOG-0218. The Journal of the National Cancer Institute paper was quite interesting, looking at microvascular density and tumoral major VEGF levels. If we can actually get these biomarkers to help aid us, as clinicians…Yes, it’s suboptimal. Yes, there are ascites. We’re all kind of guessing right now. We need help here, to really figure out which patients are going to benefit the most.

Bradley J. Monk, MD, FACS, FACOG: So, the FDA approval and the NCCN upgrade from 2b to 2a will make the reimbursement simpler. Will it change your practice?

Ursula Matulonis, MD: Yes. Right now, when patients come to us with newly-diagnosed advanced ovarian cancer, they have a lot of choices. These choices are increasing almost every few months. They have at least 5 potential clinical trials to participate in. They’ve got layering in of PARP and immuno-oncology agents. Our group still uses intraperitoneal cisplatin chemotherapy at 100 mg/m2, based upon GOG 172. We’ve got the HIPEC data. And now, there’s the use of bevacizumab. So, as a group, at Dana-Farber/Brigham and Women’s Cancer Center, we will have a discussion and come up with logical treatment plans for these patients. In some patients, we’re going to be discussing all of these different options.

Bradley J. Monk, MD, FACS, FACOG: So, let’s try to be very practical here. Let’s say you decide to do intraperitoneal chemotherapy? Does that include bevacizumab?

Ursula Matulonis, MD: Based upon GOG 172, when using 100 mg/m2 of cisplatin, it did not include bevacizumab. So, I would not include bevacizumab in those patients.

Bradley J. Monk, MD, FACS, FACOG: How about when you treat weekly? If you dose-dense weekly, does that include bevacizumab?

Shannon N. Westin, MD, MPH: At this point, no. Based on the studies that we have, we saw that the benefit of weekly is in those patients who are not getting bevacizumab. So, I feel like that’s an outstanding question—are we going to do weekly therapy, or are we going to add bevacizumab?

David O’Malley, MD: Well, it was a subanalysis. It included a very small population of patients.

Shannon N. Westin, MD, MPH: Absolutely.

David O’Malley, MD: In one trial, we now have 3 negative files looking at dose-dense therapy. I think the question on dose-dense or weekly paclitaxel is actually over. We should be using an every 3-week regimen in these patients. Bevacizumab may provide other benefit. Again, I want to identify patients who are going to have the maximum benefit of that. The subanalysis of ICON7 identifies the subgroup of patients. Again, the European component of those trials….

Bradley J. Monk, MD, FACS, FACOG: We don’t use intraperitoneal chemotherapy in Phoenix, but we do agree that weekly’s over, at least for now. I was initially an advocate of weekly, even here on OncLive®. I think weekly came and went. It’s an every 3-week world. Whether it’s every 3-weeks with intraperitoneal chemotherapy or bevacizumab, I think that’s an interesting point.

Matthew Powell, MD: The caveat considers MITO-7 data, for our more frail patients, using a weekly strategy of an AUC of 2 of carboplatin with Taxol at 60 mg/m2.

Bradley J. Monk, MD, FACS, FACOG: When I say weekly, I mean dose-dense weekly. When paclitaxel is given weekly, you can dose intensify. But, if you give it weekly, since it’s better tolerated, you can just give fractionated doses. You could drip in the chemotherapy. As I say, an AUC of 2, right?

David O’Malley, MD: Dr. Monk, weekly dose-dense Taxol is not better tolerated at 80 mg/m2.

Bradley J. Monk, MD, FACS, FACOG: Then, weekly is better tolerated. And so, when weekly is better tolerated, you can dose intensify. But at equivalent doses, it’s better tolerated. So, AUC at 2 and paclitaxel at 60 weekly is better tolerated.

David O’Malley, MD: I would agree with that. It’s nice for elderly patients.

Bradley J. Monk, MD, FACS, FACOG: But, that’s not dose-dense. That’s fractionated.

Ursula Matulonis, MD: There’s a particular situation that I will still use—carboplatin AUC 6 and weekly paclitaxel. That’s for a very ill neoadjuvant patient who comes in with lots of ascites, is super sick, and I want to see them every week. But, other than that, I agree that I am an every 3-week carboplatin/paclitaxel user.

David O’Malley, MD: I was hoping you were going to say, when you’re giving it in Japan.

Bradley J. Monk, MD, FACS, FACOG: The strong supportive trial was in Japanese women. But again, it takes 2 or more trials to convince me of anything. The weekly idea has not been substantiated, and the use of HIPEC needs a second trial, to our point.

But, we have 2 trials of bevacizumab—GOG-0218 and ICON7. Both studies published at the same time. So, again, there were concerns for trying to figure out who the best patient for bevacizumab is. I said that we have 3 challenges. One is reimbursement. The NCCN and the FDA will approve that, help that, and improve that. Then, we have this idea of, is it just a medication for what you said—ascites and liver metastases? Or, is it for all-comers, in the front line?

Ursula Matulonis, MD: I think that GOG-0218, as we see more survival data that comes out from the ASCO Annual Meeting, does support it. As long as the FDA will give us an approval, it does support the use of bevacizumab in certain patients. ICON7—for the intent-to-treat population, the overall survival difference was not different. And in that second paper, the progression-free survival was also not significant between the 2 groups. Granted, it’s a different dose of bevacizumab.

Bradley J. Monk, MD, FACS, FACOG: You mean it’s a non-placebo­–controlled trial at the wrong dose, for too short of a trial….

David O’Malley, MD: I think that might be slightly overstated. The half-life of bevacizumab is probably adequate at that dose. I think the approved dose of 50 mg, every 3 weeks is what we should be using.

Ursula Matulonis, MD: Correct. I agree.

Bradley J. Monk, MD, FACS, FACOG: Generally, in antibodies like cetuximab, we have a loading dose. So, if you’re going to use 7.5, then at least load them better....

David O’Malley, MD: Clearly, no data support that last statement.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: We have 3 challenges to filing, with GOG-0218. One is the NCCN. The second, which we’ll talk about it in a minute, is how bevacizumab now works in neoadjuvant therapy, because that wasn’t included. The third is, is this really just a high-risk opportunity—patients with stage 4, large volume residual disease—because that might be where the biggest benefit is, at least in ICON7? Is it going to change your practice, to get it FDA approved?

David O’Malley, MD: You know, it will change practice. There are a lot of regional differences between the approval of bevacizumab in the upfront setting. And so, we have a lot of trouble getting approval for bevacizumab in the upfront setting.

Bradley J. Monk, MD, FACS, FACOG: Payment, you mean?

David O’Malley, MD: Correct. That’s a good point—payment for these drugs. In those patients who I want to give bevacizumab, and you already identified those high-risk patients—large ascites, large volume disease, extra-abdominal disease—I will utilize bevacizumab. In the past, I wasn’t able to.

Bradley J. Monk, MD, FACS, FACOG: That’s interesting. How about you guys? Is it going to change your uptake?

Matthew Powell, MD: Yes. And the other thing I’m excited about is, we saw the translational science in GOG-0218. The Journal of the National Cancer Institute paper was quite interesting, looking at microvascular density and tumoral major VEGF levels. If we can actually get these biomarkers to help aid us, as clinicians…Yes, it’s suboptimal. Yes, there are ascites. We’re all kind of guessing right now. We need help here, to really figure out which patients are going to benefit the most.

Bradley J. Monk, MD, FACS, FACOG: So, the FDA approval and the NCCN upgrade from 2b to 2a will make the reimbursement simpler. Will it change your practice?

Ursula Matulonis, MD: Yes. Right now, when patients come to us with newly-diagnosed advanced ovarian cancer, they have a lot of choices. These choices are increasing almost every few months. They have at least 5 potential clinical trials to participate in. They’ve got layering in of PARP and immuno-oncology agents. Our group still uses intraperitoneal cisplatin chemotherapy at 100 mg/m2, based upon GOG 172. We’ve got the HIPEC data. And now, there’s the use of bevacizumab. So, as a group, at Dana-Farber/Brigham and Women’s Cancer Center, we will have a discussion and come up with logical treatment plans for these patients. In some patients, we’re going to be discussing all of these different options.

Bradley J. Monk, MD, FACS, FACOG: So, let’s try to be very practical here. Let’s say you decide to do intraperitoneal chemotherapy? Does that include bevacizumab?

Ursula Matulonis, MD: Based upon GOG 172, when using 100 mg/m2 of cisplatin, it did not include bevacizumab. So, I would not include bevacizumab in those patients.

Bradley J. Monk, MD, FACS, FACOG: How about when you treat weekly? If you dose-dense weekly, does that include bevacizumab?

Shannon N. Westin, MD, MPH: At this point, no. Based on the studies that we have, we saw that the benefit of weekly is in those patients who are not getting bevacizumab. So, I feel like that’s an outstanding question—are we going to do weekly therapy, or are we going to add bevacizumab?

David O’Malley, MD: Well, it was a subanalysis. It included a very small population of patients.

Shannon N. Westin, MD, MPH: Absolutely.

David O’Malley, MD: In one trial, we now have 3 negative files looking at dose-dense therapy. I think the question on dose-dense or weekly paclitaxel is actually over. We should be using an every 3-week regimen in these patients. Bevacizumab may provide other benefit. Again, I want to identify patients who are going to have the maximum benefit of that. The subanalysis of ICON7 identifies the subgroup of patients. Again, the European component of those trials….

Bradley J. Monk, MD, FACS, FACOG: We don’t use intraperitoneal chemotherapy in Phoenix, but we do agree that weekly’s over, at least for now. I was initially an advocate of weekly, even here on OncLive®. I think weekly came and went. It’s an every 3-week world. Whether it’s every 3-weeks with intraperitoneal chemotherapy or bevacizumab, I think that’s an interesting point.

Matthew Powell, MD: The caveat considers MITO-7 data, for our more frail patients, using a weekly strategy of an AUC of 2 of carboplatin with Taxol at 60 mg/m2.

Bradley J. Monk, MD, FACS, FACOG: When I say weekly, I mean dose-dense weekly. When paclitaxel is given weekly, you can dose intensify. But, if you give it weekly, since it’s better tolerated, you can just give fractionated doses. You could drip in the chemotherapy. As I say, an AUC of 2, right?

David O’Malley, MD: Dr. Monk, weekly dose-dense Taxol is not better tolerated at 80 mg/m2.

Bradley J. Monk, MD, FACS, FACOG: Then, weekly is better tolerated. And so, when weekly is better tolerated, you can dose intensify. But at equivalent doses, it’s better tolerated. So, AUC at 2 and paclitaxel at 60 weekly is better tolerated.

David O’Malley, MD: I would agree with that. It’s nice for elderly patients.

Bradley J. Monk, MD, FACS, FACOG: But, that’s not dose-dense. That’s fractionated.

Ursula Matulonis, MD: There’s a particular situation that I will still use—carboplatin AUC 6 and weekly paclitaxel. That’s for a very ill neoadjuvant patient who comes in with lots of ascites, is super sick, and I want to see them every week. But, other than that, I agree that I am an every 3-week carboplatin/paclitaxel user.

David O’Malley, MD: I was hoping you were going to say, when you’re giving it in Japan.

Bradley J. Monk, MD, FACS, FACOG: The strong supportive trial was in Japanese women. But again, it takes 2 or more trials to convince me of anything. The weekly idea has not been substantiated, and the use of HIPEC needs a second trial, to our point.

But, we have 2 trials of bevacizumab—GOG-0218 and ICON7. Both studies published at the same time. So, again, there were concerns for trying to figure out who the best patient for bevacizumab is. I said that we have 3 challenges. One is reimbursement. The NCCN and the FDA will approve that, help that, and improve that. Then, we have this idea of, is it just a medication for what you said—ascites and liver metastases? Or, is it for all-comers, in the front line?

Ursula Matulonis, MD: I think that GOG-0218, as we see more survival data that comes out from the ASCO Annual Meeting, does support it. As long as the FDA will give us an approval, it does support the use of bevacizumab in certain patients. ICON7—for the intent-to-treat population, the overall survival difference was not different. And in that second paper, the progression-free survival was also not significant between the 2 groups. Granted, it’s a different dose of bevacizumab.

Bradley J. Monk, MD, FACS, FACOG: You mean it’s a non-placebo­–controlled trial at the wrong dose, for too short of a trial….

David O’Malley, MD: I think that might be slightly overstated. The half-life of bevacizumab is probably adequate at that dose. I think the approved dose of 50 mg, every 3 weeks is what we should be using.

Ursula Matulonis, MD: Correct. I agree.

Bradley J. Monk, MD, FACS, FACOG: Generally, in antibodies like cetuximab, we have a loading dose. So, if you’re going to use 7.5, then at least load them better....

David O’Malley, MD: Clearly, no data support that last statement.

Transcript Edited for Clarity 
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