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Bevacizumab Use in Angiogenesis Clinical Practice

Panelists:Johanna C. Bendell, MD, Sarah Cannon Research Institute; Edward Garon, MD, Jonsson Comprehensive Cancer Center at UCLA; Roy Herbst, MD, Yale School of Medicine; Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Manish Shah, MD, Weill Cornell Medical College; Mark Socinski, MD, University of Pittsburgh
Published: Wednesday, May 04, 2016


Transcript:

Mark A. Socinski, MD:
So, let’s talk a little bit about clinical practice and where we use it. I’ll ask Dr. Garon to kind of give us, with regard to bevacizumab, how you use this agent in your clinical practice.

Edward Garon, MD: Sure. So, bevacizumab was approved with a very specific chemotherapy backbone, and that was with carboplatin and paclitaxel, which is a standard chemotherapeutic option here in the United States. It was, interestingly, not necessarily the standard chemotherapeutic option that was being used in Europe at the time. And, in fact, when they did randomize to a chemotherapeutic regimen that was used more traditionally in Europe—that of cisplatin and gemcitabine—there was not a survival advantage.

In the United States, many people have used carboplatin/paclitaxel and bevacizumab. And I think it is still yet to be seen whether there is anything particularly special about that regimen. We know that at least there was another regimen where it was not evaluated, and, as you know, we were both part of the PointBreak study. In that study, there was a comparison between carboplatin/paclitaxel and bevacizumab compared with carboplatin/pemetrexed and bevacizumab. There, there was no difference. People have used that data to draw many different conclusions. And if you talk to different people, they tend to draw very different conclusions from that data set.

So, in my personal practice, I traditionally went ahead and used bevacizumab, have used it with carboplatin and paclitaxel in the frontline setting. Although, certainly, when I see consultations and second opinion, I still see many patients who do use that PointBreak regimen of carboplatin/pemetrexed and bevacizumab, although that has not been my personal choice in terms of therapy.

Mark A. Socinski, MD: Roy, your thoughts about how there’s lots of discussion about the bevacizumab-eligible patient in lung cancer. We have the histology issue. We have the hemoptysis issue. Tell us kind of the factors that you go through in your head, in terms of who gets it and what are the factors that would make you not give it.

Roy S. Herbst, MD, PhD: Eddy gave a good summary. I think that in lung cancer, it really is the non-squamous patients that traditionally are the ones that we consider bevacizumab-eligible. And that’s probably how I use it most in practice, in someone who has non-squamous cell cancer who’s not eligible for a protocol. You know we have so many new protocols. But I probably would give them the carboplatin/paclitaxel with bevacizumab. I’ve become very comfortable with using that as per the ECOG trial.

We did do a trial in SWOG with cetuximab, bevacizumab, and chemotherapy looking at some biomarker work. And there we had a little bit more of a broad sort of application of this. Someone could be bevacizumab-eligible. We looked at their age, and people could make the patients bevacizumab-ineligible if in fact they felt the patient was frail, if there were other comorbidities. Certainly, anyone who has any history of bleeding—hemoptysis—you wouldn’t put those patients on it. If you really wanted to use the drug, though, I think the patients that would have the issues with the hemoptysis tend to be those with the centrally located masses. But is there a compelling reason to use the drug? No, I’m not sure. But if there was, I think you could say you could take a squamous patient who didn’t have any central lesions.

Mark A. Socinski, MD: Intrathoracic disease, yes.

Roy S. Herbst, MD, PhD: And you could use it.

Mark A. Socinski, MD: Because they were included in some of the registries.

Roy S. Herbst, MD, PhD: They were included in some of the registries post approval.

Mark A. Socinski, MD: Yes. Dr. Bendell, in colon cancer, where does bevacizumab fit into your treatment?

Johanna Bendell, MD: It’s like water for colon cancer, certainly in the first-line metastatic setting. So, first-line setting with chemotherapy backbones—FOLFIRI, FOLFOX—and to the second-line setting you can continue on with bevacizumab. There’s also different choices of ramucirumab, which has a positive survival advantage. We have the VEGF-Trap, aflibercept, which is also approved there. And then even further down, the tyrosine kinase inhibitor, regorafenib, also has approval in the third-line setting. So, certainly, with colon cancer specifically, we’ve seen the continuation of antiangiogenic therapy through multiple lines.

Mark A. Socinski, MD: At least three, right?

Johanna Bendell, MD: Yes.

Mark A. Socinski, MD: Yes. Dr. Shah, your thoughts?

Manish A. Shah, MD: So, in terms of the people who are not really eligible for bevacizumab, at least in GI cancers, we know there’s a slightly higher risk of arterial thromboembolic events, so myocardial infarction and stroke. And so people who are older, people who have those risk factors, people who’ve had prior history of stroke or MI, we tend to avoid it a little bit. I think that with the approval in the second-line setting, as well as with the continuation, there are instances where you may not want to do it in the up-front setting. For example, if you’re planning on metastasectomy and you don’t want to have any issues with regard to wound healing, you may not have initially given the bevacizumab but choose to give it afterwards. So, those are some of the considerations, as well.

Transcript Edited for Clarity
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Transcript:

Mark A. Socinski, MD:
So, let’s talk a little bit about clinical practice and where we use it. I’ll ask Dr. Garon to kind of give us, with regard to bevacizumab, how you use this agent in your clinical practice.

Edward Garon, MD: Sure. So, bevacizumab was approved with a very specific chemotherapy backbone, and that was with carboplatin and paclitaxel, which is a standard chemotherapeutic option here in the United States. It was, interestingly, not necessarily the standard chemotherapeutic option that was being used in Europe at the time. And, in fact, when they did randomize to a chemotherapeutic regimen that was used more traditionally in Europe—that of cisplatin and gemcitabine—there was not a survival advantage.

In the United States, many people have used carboplatin/paclitaxel and bevacizumab. And I think it is still yet to be seen whether there is anything particularly special about that regimen. We know that at least there was another regimen where it was not evaluated, and, as you know, we were both part of the PointBreak study. In that study, there was a comparison between carboplatin/paclitaxel and bevacizumab compared with carboplatin/pemetrexed and bevacizumab. There, there was no difference. People have used that data to draw many different conclusions. And if you talk to different people, they tend to draw very different conclusions from that data set.

So, in my personal practice, I traditionally went ahead and used bevacizumab, have used it with carboplatin and paclitaxel in the frontline setting. Although, certainly, when I see consultations and second opinion, I still see many patients who do use that PointBreak regimen of carboplatin/pemetrexed and bevacizumab, although that has not been my personal choice in terms of therapy.

Mark A. Socinski, MD: Roy, your thoughts about how there’s lots of discussion about the bevacizumab-eligible patient in lung cancer. We have the histology issue. We have the hemoptysis issue. Tell us kind of the factors that you go through in your head, in terms of who gets it and what are the factors that would make you not give it.

Roy S. Herbst, MD, PhD: Eddy gave a good summary. I think that in lung cancer, it really is the non-squamous patients that traditionally are the ones that we consider bevacizumab-eligible. And that’s probably how I use it most in practice, in someone who has non-squamous cell cancer who’s not eligible for a protocol. You know we have so many new protocols. But I probably would give them the carboplatin/paclitaxel with bevacizumab. I’ve become very comfortable with using that as per the ECOG trial.

We did do a trial in SWOG with cetuximab, bevacizumab, and chemotherapy looking at some biomarker work. And there we had a little bit more of a broad sort of application of this. Someone could be bevacizumab-eligible. We looked at their age, and people could make the patients bevacizumab-ineligible if in fact they felt the patient was frail, if there were other comorbidities. Certainly, anyone who has any history of bleeding—hemoptysis—you wouldn’t put those patients on it. If you really wanted to use the drug, though, I think the patients that would have the issues with the hemoptysis tend to be those with the centrally located masses. But is there a compelling reason to use the drug? No, I’m not sure. But if there was, I think you could say you could take a squamous patient who didn’t have any central lesions.

Mark A. Socinski, MD: Intrathoracic disease, yes.

Roy S. Herbst, MD, PhD: And you could use it.

Mark A. Socinski, MD: Because they were included in some of the registries.

Roy S. Herbst, MD, PhD: They were included in some of the registries post approval.

Mark A. Socinski, MD: Yes. Dr. Bendell, in colon cancer, where does bevacizumab fit into your treatment?

Johanna Bendell, MD: It’s like water for colon cancer, certainly in the first-line metastatic setting. So, first-line setting with chemotherapy backbones—FOLFIRI, FOLFOX—and to the second-line setting you can continue on with bevacizumab. There’s also different choices of ramucirumab, which has a positive survival advantage. We have the VEGF-Trap, aflibercept, which is also approved there. And then even further down, the tyrosine kinase inhibitor, regorafenib, also has approval in the third-line setting. So, certainly, with colon cancer specifically, we’ve seen the continuation of antiangiogenic therapy through multiple lines.

Mark A. Socinski, MD: At least three, right?

Johanna Bendell, MD: Yes.

Mark A. Socinski, MD: Yes. Dr. Shah, your thoughts?

Manish A. Shah, MD: So, in terms of the people who are not really eligible for bevacizumab, at least in GI cancers, we know there’s a slightly higher risk of arterial thromboembolic events, so myocardial infarction and stroke. And so people who are older, people who have those risk factors, people who’ve had prior history of stroke or MI, we tend to avoid it a little bit. I think that with the approval in the second-line setting, as well as with the continuation, there are instances where you may not want to do it in the up-front setting. For example, if you’re planning on metastasectomy and you don’t want to have any issues with regard to wound healing, you may not have initially given the bevacizumab but choose to give it afterwards. So, those are some of the considerations, as well.

Transcript Edited for Clarity
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