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Bevacizumab in Recurrent 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: Histologic subtype, platinum-free interval, number of lines of therapy, molecular signature, preexisting toxicities, and the goals of therapy—thank you. So, to the point, the approval of bevacizumab in recurrent ovarian cancer is based on this antiquated nomenclature of platinum-resistant and platinum-sensitive recurrence. Can you tell us about the current approval of bevacizumab in recurrent disease?

Shannon N. Westin, MD, MPH: Absolutely. Basically, you can use it whenever you want, right? We can use it in the so-called platinum-sensitive setting, which just means that they’ve had a long interval since their last platinum. That’s in combination with chemotherapy, whether that be paclitaxel and carboplatin or gemcitabine and carboplatin. Certainly, you can add bevacizumab to the chemotherapy in induction to try to get yourself a better response rate. Then you can proceed with bevacizumab as a maintenance strategy. Or, in using the antiquated terms, if you do have a patient whose tumor has progressed pretty shortly after the completion of primary therapy, you can consider bevacizumab in addition to a single-agent chemotherapy, such as pegylated liposomal doxorubicin, paclitaxel, or topotecan.

Bradley J. Monk, MD, FACS, FACOG: Five FDA-approved chemotherapy backbones—and then I have our single medical oncologist on the panel.

Matthew Powell, MD: We’re all becoming medical oncologists.

Shannon N. Westin, MD, MPH: I was going to say that.

Matthew Powell, MD: We operate less and less. We’re all becoming medical oncologists.

Bradley J. Monk, MD, FACS, FACOG: I don’t actually like to be called a surgeon who gives chemotherapy. I’m a medical oncologist who operates. We operate less and less, and we give more and more chemotherapy.

Matthew Powell, MD: And we’re becoming immuno-biologists.

Bradley J. Monk, MD, FACS, FACOG: Ursula, is bevacizumab a better frontline drug or a better second-line drug, with the assumption that we’ll soon have an FDA frontline approval?

Ursula Matulonis, MD: That’s a great question. I think the GOG-0218 overall survival data are going to inform us on that. We will soon know if there is a really compelling reason to use bevacizumab up front, where I can say to a patient, “I’m going to be able to improve your survival by using bevacizumab.”  

Then we use bevacizumab in certain clinical situations within the recurrent setting. I tend to use more bevacizumab for platinum-resistant disease, just because of the 2 regimens that Shannon’s already mentioned—carboplatin/Taxol/bevacizumab or carboplatin/gemcitabine/bevacizumab. So, reusing Taxol—patients don’t really love to reuse paclitaxel so soon after they have just had their hair grow back, or they’ve got some neuropathy. With carboplatin/gemcitabine/bevacizumab, there are certain situations where I’ve used it. But there’s no overall survival benefit, and the progression-free survival benefit is around 4 months. In the platinum-resistant setting, I do think that the weekly paclitaxel/bevacizumab results are special. They’re outstanding.

Bradley J. Monk, MD, FACS, FACOG: And maybe even nab-paclitaxel?

Ursula Matulonis, MD: It’s noteworthy.

Bradley J. Monk, MD, FACS, FACOG: So, the hazard ratios are better in recurrent disease, but the median differences are better in the frontline setting?

Ursula Matulonis, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: So, if you’re in the median, the close to 6 months, frontline, is certainly better than the 4 months in sensitive disease and 3 months in resistant disease, but the hazard ratio is much better in recurrent disease.

Matthew Powell, MD: You know, the bevacizumab with topotecan hazard ratio looks fantastic, but I don’t think that we’re necessarily going to jump on that regimen.

Bradley J. Monk, MD, FACS, FACOG: Maybe the risk of gastrointestinal perforation is higher in recurrent disease? Although, as I think you said, Dave, the risk of gastrointestinal perforation is becoming lower and lower because we understand the medication. We’re more advanced.

David O’Malley, MD: We understand the patients who are considered to be higher risk.

Bradley J. Monk, MD, FACS, FACOG: And when you use it in the frontline setting, there are more cycles. If there are more cycles, the cost increases in the frontline, so I think the magnitude of the benefit will be important as value is added.

David O’Malley, MD: Now, cost is more than just actual cost. We know there’s cumulative toxicity with bevacizumab—hypertension and renal dysfunction. The cost is not just the actual dollar amount. The cost is to the patient and their ability to receive other chemotherapies in the future, so that does have to come into play, particularly for somebody with renal toxicity.

Transcript Edited for Clarity 

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Transcript: 

Bradley J. Monk, MD, FACS, FACOG: Histologic subtype, platinum-free interval, number of lines of therapy, molecular signature, preexisting toxicities, and the goals of therapy—thank you. So, to the point, the approval of bevacizumab in recurrent ovarian cancer is based on this antiquated nomenclature of platinum-resistant and platinum-sensitive recurrence. Can you tell us about the current approval of bevacizumab in recurrent disease?

Shannon N. Westin, MD, MPH: Absolutely. Basically, you can use it whenever you want, right? We can use it in the so-called platinum-sensitive setting, which just means that they’ve had a long interval since their last platinum. That’s in combination with chemotherapy, whether that be paclitaxel and carboplatin or gemcitabine and carboplatin. Certainly, you can add bevacizumab to the chemotherapy in induction to try to get yourself a better response rate. Then you can proceed with bevacizumab as a maintenance strategy. Or, in using the antiquated terms, if you do have a patient whose tumor has progressed pretty shortly after the completion of primary therapy, you can consider bevacizumab in addition to a single-agent chemotherapy, such as pegylated liposomal doxorubicin, paclitaxel, or topotecan.

Bradley J. Monk, MD, FACS, FACOG: Five FDA-approved chemotherapy backbones—and then I have our single medical oncologist on the panel.

Matthew Powell, MD: We’re all becoming medical oncologists.

Shannon N. Westin, MD, MPH: I was going to say that.

Matthew Powell, MD: We operate less and less. We’re all becoming medical oncologists.

Bradley J. Monk, MD, FACS, FACOG: I don’t actually like to be called a surgeon who gives chemotherapy. I’m a medical oncologist who operates. We operate less and less, and we give more and more chemotherapy.

Matthew Powell, MD: And we’re becoming immuno-biologists.

Bradley J. Monk, MD, FACS, FACOG: Ursula, is bevacizumab a better frontline drug or a better second-line drug, with the assumption that we’ll soon have an FDA frontline approval?

Ursula Matulonis, MD: That’s a great question. I think the GOG-0218 overall survival data are going to inform us on that. We will soon know if there is a really compelling reason to use bevacizumab up front, where I can say to a patient, “I’m going to be able to improve your survival by using bevacizumab.”  

Then we use bevacizumab in certain clinical situations within the recurrent setting. I tend to use more bevacizumab for platinum-resistant disease, just because of the 2 regimens that Shannon’s already mentioned—carboplatin/Taxol/bevacizumab or carboplatin/gemcitabine/bevacizumab. So, reusing Taxol—patients don’t really love to reuse paclitaxel so soon after they have just had their hair grow back, or they’ve got some neuropathy. With carboplatin/gemcitabine/bevacizumab, there are certain situations where I’ve used it. But there’s no overall survival benefit, and the progression-free survival benefit is around 4 months. In the platinum-resistant setting, I do think that the weekly paclitaxel/bevacizumab results are special. They’re outstanding.

Bradley J. Monk, MD, FACS, FACOG: And maybe even nab-paclitaxel?

Ursula Matulonis, MD: It’s noteworthy.

Bradley J. Monk, MD, FACS, FACOG: So, the hazard ratios are better in recurrent disease, but the median differences are better in the frontline setting?

Ursula Matulonis, MD: Yes.

Bradley J. Monk, MD, FACS, FACOG: So, if you’re in the median, the close to 6 months, frontline, is certainly better than the 4 months in sensitive disease and 3 months in resistant disease, but the hazard ratio is much better in recurrent disease.

Matthew Powell, MD: You know, the bevacizumab with topotecan hazard ratio looks fantastic, but I don’t think that we’re necessarily going to jump on that regimen.

Bradley J. Monk, MD, FACS, FACOG: Maybe the risk of gastrointestinal perforation is higher in recurrent disease? Although, as I think you said, Dave, the risk of gastrointestinal perforation is becoming lower and lower because we understand the medication. We’re more advanced.

David O’Malley, MD: We understand the patients who are considered to be higher risk.

Bradley J. Monk, MD, FACS, FACOG: And when you use it in the frontline setting, there are more cycles. If there are more cycles, the cost increases in the frontline, so I think the magnitude of the benefit will be important as value is added.

David O’Malley, MD: Now, cost is more than just actual cost. We know there’s cumulative toxicity with bevacizumab—hypertension and renal dysfunction. The cost is not just the actual dollar amount. The cost is to the patient and their ability to receive other chemotherapies in the future, so that does have to come into play, particularly for somebody with renal toxicity.

Transcript Edited for Clarity 
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