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When to Add Bevacizumab for Recurrent Ovarian Cancer

Panelists: Bradley J. Monk, MD, University of Arizona and Creighton University; Robert L. Coleman, MD, MD Anderson Cancer Center; Gottfried E. Konecny, MD, University of California, Los Angeles; Katie Moore, MD, University of Oklahoma; Matthew A. Powell, MD, Washington University in St. Louis
Published: Tuesday, Aug 08, 2017



Transcript:

Bradley J. Monk, MD: We discussed the considerations in treating recurrent disease. We’ve discussed the role of surgery. Clearly, chemotherapy plays a major role in treating recurrent ovarian cancer. We now have bevacizumab approved with 5 chemotherapy backbones: 3 in platinum-resistant disease, 2 in platinum-sensitive disease. Have these approvals, Katie, changed your practice? Or were you like Matt, with the secondary debulking idea, “Well, I was right already, and these confirm that I was right.” And it’s weird that you don’t have to go through the same authorization for a secondary debulking that she has to go through to get bevacizumab.

Matthew A. Powell, MD: Not at all.

Katie Moore, MD: Absolutely.

Bradley J. Monk, MD: Even though surgery is probably as expensive or more expensive. It’s interesting, right? So, has the approval of bevacizumab changed your practice?

Katie Moore, MD: It has definitely change my practice, and I think I’m still evolving. We now have maintenance drugs approved. We did not have maintenance drugs approved before, and so I think the standard of care was observation. You get to a complete response, observation. You get a good partial response, maybe observation, maybe I just keep the carboplatin going indefinitely. Now I have maintenance options, and so I’m counseling patients better. Because we have the studies and we’ve looked back at our history, personally, I have a better understanding of this population, and they don’t do as well. They don’t last as long off of therapy as we think that they do.

Bradley J. Monk, MD: Which patients don’t last?

Katie Moore, MD: Platinum sensitive. You get a response and take them off the study. Of course, you’re going to have your outliers, but for the most part, they recur not 2 years later, not 1 year...

Bradley J. Monk, MD: It’s 9-and-a-half months.

Katie Moore, MD: So, I look at that and I say, “Well, maybe this makes more sense than that. I think I’ve changed my tune on that.”

Bradley J. Monk, MD: So, let me summarize. The platinum-sensitive approval includes bevacizumab with chemotherapy and then bevacizumab maintenance.

Katie Moore, MD: Right. And we have an approval for niraparib.

Bradley J. Monk, MD: Right. In that same setting?

Katie Moore, MD: In the same setting. And so, now we have 2 drugs, I have a patient in front of me, and I don’t have good data on which to pick. We get into the sequencing question of, what do I use first? And it comes down to the residual toxicities—what’s her molecular profile? Even though niraparib does not require the presence of HRD, I think it does tell us who’s going to respond better versus bevacizumab, which has an overall survival advantage. So, what do you pick?

Bradley J. Monk, MD: Matt, what’s the role of bevacizumab in your practice?

Matthew A. Powell, MD: Well, I would tell you that GOG-213 changed things for me.

Bradley J. Monk, MD: Tell us what GOG-213 is—or, Rob, you’re the PI, let’s have him tell us what is.

Matthew A. Powell, MD: That would be hard for me to do right in front of the expert.

Bradley J. Monk, MD: Rob, tell us what GOG-213 is and then, Matt, you tell us what the role of bevacizumab is in your practice.

Robert L. Coleman, MD: GOG-213 is a randomized trial that has 2 primary endpoints. The first is whether or not bevacizumab added to chemotherapy improves overall survival, and the second is whether or not surgery improves overall survival in the context of chemotherapy.

Bradley J. Monk, MD: How big is that trial?

Robert L. Coleman, MD: For the chemotherapy, the first objective, the one that was just published and reported, was 674 patients randomized equally between paclitaxel/carboplatinum, the only chemotherapy we allowed in the trial, versus paclitaxel/carboplatinum/bevacizumab followed by bevacizumab maintenance to progression. So, the primary endpoint was overall survival. It showed a hazard ratio of about 0.83—0.82 to 0.83—for improvement in overall survival and a median of about 5 months. And then, of course, the other secondary endpoints, such as PFS, were extended, the response rate was extended.

Bradley J. Monk, MD: The response rate is 75%.

Robert L. Coleman, MD: Yes, and I think, even more importantly, the complete response rate was doubled.

Bradley J. Monk, MD: So, bevacizumab increases the overall response rate by 20% and then doubles the CR rate.

Robert L. Coleman, MD: Right. And it was important—of course, because many patients were on these therapies for long periods of time—that the safety signal is very similar to what we had seen with ICON7 and GOG-218. So, there are no new safety signals.

Bradley J. Monk, MD: Matt, there are 2 opinions. Some people say, “I love bevacizumab, platinum-sensitive relapse. I’m going to use it, give a maintenance phase, get a prolonged OS for maybe 5 months, and definitely increase the response rate by 20%.” That’s one thought. The other thought is, “I’m going to save it ‘til she really needs it. When she has ascites, when she has platinum-resistant disease, it’s going to be fewer cycles.” The other option is, “Look, the incremental benefit of bevacizumab is trivial, it’s too expensive and too toxic. I’m never going to use it.” Where do you put that?

Matthew A. Powell, MD: Had it not affected overall survival in the United States—this study was done in the United States—where we gave bevacizumab later in probably the vast majority of patients who were in the control arm.

Robert L. Coleman, MD: One-third.

Bradley J. Monk, MD: One-third crossed over.

Matthew A. Powell, MD: So, the strategy that you’re saying, for me, I can’t fix that by giving that chemotherapy later. They’re not going to get that survival benefit, it looks to me. There’s some unique interaction between Taxol (paclitaxel) and bevacizumab in my mind.

Bradley J. Monk, MD: That’s what I think.

Matthew A. Powell, MD: There is more to the story than we completely understand. If you look at the AURELIA trial, the taxane/bevacizumab arm is very exciting. But moving things forward to GOG-213, I think really changes practice. We’re not using the AGO regimen, we’re not use the CALYPSO regimen nearly as much.

Bradley J. Monk, MD: Carboplatin/PLD (pegylated liposomal doxorubicin), yes.

Matthew A. Powell, MD: And going back to Taxol, it obviously means some hair loss and that means neuropathy for the patients. But I think you can show survival benefit, where patients are actually living longer.

Bradley J. Monk, MD: So, that’s a great summary.

Gottfried E. Konecny, MD: Don’t you think a way around that would be to do correlative studies and find whether or not there are specific subsets that really have the greatest impact?

Robert L. Coleman, MD: Absolutely.

Bradley J. Monk, MD: Absolutely.

Gottfried E. Konecny, MD: Not each ovarian cancer is the same.

Bradley J. Monk, MD: We’re working on it.

Robert L. Coleman, MD: Totally working on it. Yes, you’re absolutely right.

Transcript Edited for Clarity

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Transcript:

Bradley J. Monk, MD: We discussed the considerations in treating recurrent disease. We’ve discussed the role of surgery. Clearly, chemotherapy plays a major role in treating recurrent ovarian cancer. We now have bevacizumab approved with 5 chemotherapy backbones: 3 in platinum-resistant disease, 2 in platinum-sensitive disease. Have these approvals, Katie, changed your practice? Or were you like Matt, with the secondary debulking idea, “Well, I was right already, and these confirm that I was right.” And it’s weird that you don’t have to go through the same authorization for a secondary debulking that she has to go through to get bevacizumab.

Matthew A. Powell, MD: Not at all.

Katie Moore, MD: Absolutely.

Bradley J. Monk, MD: Even though surgery is probably as expensive or more expensive. It’s interesting, right? So, has the approval of bevacizumab changed your practice?

Katie Moore, MD: It has definitely change my practice, and I think I’m still evolving. We now have maintenance drugs approved. We did not have maintenance drugs approved before, and so I think the standard of care was observation. You get to a complete response, observation. You get a good partial response, maybe observation, maybe I just keep the carboplatin going indefinitely. Now I have maintenance options, and so I’m counseling patients better. Because we have the studies and we’ve looked back at our history, personally, I have a better understanding of this population, and they don’t do as well. They don’t last as long off of therapy as we think that they do.

Bradley J. Monk, MD: Which patients don’t last?

Katie Moore, MD: Platinum sensitive. You get a response and take them off the study. Of course, you’re going to have your outliers, but for the most part, they recur not 2 years later, not 1 year...

Bradley J. Monk, MD: It’s 9-and-a-half months.

Katie Moore, MD: So, I look at that and I say, “Well, maybe this makes more sense than that. I think I’ve changed my tune on that.”

Bradley J. Monk, MD: So, let me summarize. The platinum-sensitive approval includes bevacizumab with chemotherapy and then bevacizumab maintenance.

Katie Moore, MD: Right. And we have an approval for niraparib.

Bradley J. Monk, MD: Right. In that same setting?

Katie Moore, MD: In the same setting. And so, now we have 2 drugs, I have a patient in front of me, and I don’t have good data on which to pick. We get into the sequencing question of, what do I use first? And it comes down to the residual toxicities—what’s her molecular profile? Even though niraparib does not require the presence of HRD, I think it does tell us who’s going to respond better versus bevacizumab, which has an overall survival advantage. So, what do you pick?

Bradley J. Monk, MD: Matt, what’s the role of bevacizumab in your practice?

Matthew A. Powell, MD: Well, I would tell you that GOG-213 changed things for me.

Bradley J. Monk, MD: Tell us what GOG-213 is—or, Rob, you’re the PI, let’s have him tell us what is.

Matthew A. Powell, MD: That would be hard for me to do right in front of the expert.

Bradley J. Monk, MD: Rob, tell us what GOG-213 is and then, Matt, you tell us what the role of bevacizumab is in your practice.

Robert L. Coleman, MD: GOG-213 is a randomized trial that has 2 primary endpoints. The first is whether or not bevacizumab added to chemotherapy improves overall survival, and the second is whether or not surgery improves overall survival in the context of chemotherapy.

Bradley J. Monk, MD: How big is that trial?

Robert L. Coleman, MD: For the chemotherapy, the first objective, the one that was just published and reported, was 674 patients randomized equally between paclitaxel/carboplatinum, the only chemotherapy we allowed in the trial, versus paclitaxel/carboplatinum/bevacizumab followed by bevacizumab maintenance to progression. So, the primary endpoint was overall survival. It showed a hazard ratio of about 0.83—0.82 to 0.83—for improvement in overall survival and a median of about 5 months. And then, of course, the other secondary endpoints, such as PFS, were extended, the response rate was extended.

Bradley J. Monk, MD: The response rate is 75%.

Robert L. Coleman, MD: Yes, and I think, even more importantly, the complete response rate was doubled.

Bradley J. Monk, MD: So, bevacizumab increases the overall response rate by 20% and then doubles the CR rate.

Robert L. Coleman, MD: Right. And it was important—of course, because many patients were on these therapies for long periods of time—that the safety signal is very similar to what we had seen with ICON7 and GOG-218. So, there are no new safety signals.

Bradley J. Monk, MD: Matt, there are 2 opinions. Some people say, “I love bevacizumab, platinum-sensitive relapse. I’m going to use it, give a maintenance phase, get a prolonged OS for maybe 5 months, and definitely increase the response rate by 20%.” That’s one thought. The other thought is, “I’m going to save it ‘til she really needs it. When she has ascites, when she has platinum-resistant disease, it’s going to be fewer cycles.” The other option is, “Look, the incremental benefit of bevacizumab is trivial, it’s too expensive and too toxic. I’m never going to use it.” Where do you put that?

Matthew A. Powell, MD: Had it not affected overall survival in the United States—this study was done in the United States—where we gave bevacizumab later in probably the vast majority of patients who were in the control arm.

Robert L. Coleman, MD: One-third.

Bradley J. Monk, MD: One-third crossed over.

Matthew A. Powell, MD: So, the strategy that you’re saying, for me, I can’t fix that by giving that chemotherapy later. They’re not going to get that survival benefit, it looks to me. There’s some unique interaction between Taxol (paclitaxel) and bevacizumab in my mind.

Bradley J. Monk, MD: That’s what I think.

Matthew A. Powell, MD: There is more to the story than we completely understand. If you look at the AURELIA trial, the taxane/bevacizumab arm is very exciting. But moving things forward to GOG-213, I think really changes practice. We’re not using the AGO regimen, we’re not use the CALYPSO regimen nearly as much.

Bradley J. Monk, MD: Carboplatin/PLD (pegylated liposomal doxorubicin), yes.

Matthew A. Powell, MD: And going back to Taxol, it obviously means some hair loss and that means neuropathy for the patients. But I think you can show survival benefit, where patients are actually living longer.

Bradley J. Monk, MD: So, that’s a great summary.

Gottfried E. Konecny, MD: Don’t you think a way around that would be to do correlative studies and find whether or not there are specific subsets that really have the greatest impact?

Robert L. Coleman, MD: Absolutely.

Bradley J. Monk, MD: Absolutely.

Gottfried E. Konecny, MD: Not each ovarian cancer is the same.

Bradley J. Monk, MD: We’re working on it.

Robert L. Coleman, MD: Totally working on it. Yes, you’re absolutely right.

Transcript Edited for Clarity
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