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Ovarian Cancer: A New Indication for Bevacizumab

Thomas Herzog, MD
Published: Monday, Apr 24, 2017



Transcript:

Thomas Herzog, MD:
Things have changed tremendously in terms of how we treat ovarian cancer patients. We tend to use the same primary backbone of a platinum with taxane, and that actually changed while I was early in training. So, that has pretty much been the backbone of our treatments throughout the course of my career. What we’ve really done, though, is seen a number of new agents come online whose combined contribution of progression-free survival has contributed to an overall survival benefit. If we look 20-plus years ago, many of these patients that had advanced disease were living in the neighborhood a little over 2 years. We then saw that extended out over 3 years with taxanes, and now we see patients, who were able to get to small volume or no gross disease at primary site of reduction, living out over 5 years in terms of median survival.

So, while we’re not curing a lot more women with ovarian cancer, we are getting these patients to live for a longer period of time. And I would argue with a better quality of life as well. I think that has been something I’ve seen as well. We’ve looked at schedules, we looked at dosing, we looked at sequencing, and as well as support during treatment, and we’ve been able to get patients through these treatments with less lingering quality of life issues, and that’s really important.

The recent approval of bevacizumab has been very welcomed by the treating community because it gives us more options. And so, with having the ability with platinum-sensitive disease to incorporate bevacizumab, it gives us the ability to put an active agent further up in the treatment line, which I think is very appealing. It also helps us address why the patient’s being treated. In other words, if the patient is symptomatic, if she has pleural effusions, ascites, all these types of hallmarks of markers for potential bevacizumab response, it gives us more in the way of a larger menu to choose from, and I think it helps us more precisely sequence these agents as we go through treatment.

The approval of bevacizumab in the platinum-sensitive space was based on 2 large phase III trials. The first trial is GOG-213. This trial looked at taking patients in the bi-factorial design through 2 decision points. The first one is, is the patient a candidate for surgery for secondary cytoreduction? So, these are platinum-sensitive patients, again, recurring out over 6 months from the time of their initial platinum. These patients were then randomized if they were surgical candidates to surgery or not having surgery, and then there was a secondary randomization between carboplatin and paclitaxel with or without the administration of bevacizumab. So, they were randomized to either receive bevacizumab with the carboplatin/paclitaxel backbone or not. Carboplatin was administered in an AUC of 5, the paclitaxel was administered at 175 mg/m2, and the bevacizumab was given at 15 mg/kg.

They found that there was an improvement in overall survival that was approximately 42.6 versus 37.3 months in terms of the medians. The hazard ratio was 0.84 or 0.82, depending on how it was calculated. That achieved barely statistical significance when you did the one based off the electronic case report forms. So, this was a very important study because we actually now have an improvement of almost 5 months in overall survival, which is very welcomed. The other thing that’s really important to point out is that you had a higher response rate as well, about 78% versus 57%.

The second phase III trial was an older trial, but it looked at carboplatin and gemcitabine. Carboplatin was given in an AUC of 4, the gemcitabine was given at 1000 mg/m2 combined with bevacizumab at the same dose as the GOG-213 trial. The OCEANS trial was with gemcitabine. And what we found was there an improvement in progression-free survival of about 4 months. Again, we saw the same increase in response rate—about 56% all the way up to 78% when you added the bevacizumab. So, very positive data.

If you look at the hazard ratio for the primary endpoint, it was 0.46—a very large benefit to receiving the bevacizumab in this case. Both of these trials are interesting because the bevacizumab was continued until disease progression or until toxicity. So, I think in terms of, how do you administer the bevacizumab? The advice would be to continue therapy until either of those 2 endpoints occurs.

Transcript Edited for Clarity
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Transcript:

Thomas Herzog, MD:
Things have changed tremendously in terms of how we treat ovarian cancer patients. We tend to use the same primary backbone of a platinum with taxane, and that actually changed while I was early in training. So, that has pretty much been the backbone of our treatments throughout the course of my career. What we’ve really done, though, is seen a number of new agents come online whose combined contribution of progression-free survival has contributed to an overall survival benefit. If we look 20-plus years ago, many of these patients that had advanced disease were living in the neighborhood a little over 2 years. We then saw that extended out over 3 years with taxanes, and now we see patients, who were able to get to small volume or no gross disease at primary site of reduction, living out over 5 years in terms of median survival.

So, while we’re not curing a lot more women with ovarian cancer, we are getting these patients to live for a longer period of time. And I would argue with a better quality of life as well. I think that has been something I’ve seen as well. We’ve looked at schedules, we looked at dosing, we looked at sequencing, and as well as support during treatment, and we’ve been able to get patients through these treatments with less lingering quality of life issues, and that’s really important.

The recent approval of bevacizumab has been very welcomed by the treating community because it gives us more options. And so, with having the ability with platinum-sensitive disease to incorporate bevacizumab, it gives us the ability to put an active agent further up in the treatment line, which I think is very appealing. It also helps us address why the patient’s being treated. In other words, if the patient is symptomatic, if she has pleural effusions, ascites, all these types of hallmarks of markers for potential bevacizumab response, it gives us more in the way of a larger menu to choose from, and I think it helps us more precisely sequence these agents as we go through treatment.

The approval of bevacizumab in the platinum-sensitive space was based on 2 large phase III trials. The first trial is GOG-213. This trial looked at taking patients in the bi-factorial design through 2 decision points. The first one is, is the patient a candidate for surgery for secondary cytoreduction? So, these are platinum-sensitive patients, again, recurring out over 6 months from the time of their initial platinum. These patients were then randomized if they were surgical candidates to surgery or not having surgery, and then there was a secondary randomization between carboplatin and paclitaxel with or without the administration of bevacizumab. So, they were randomized to either receive bevacizumab with the carboplatin/paclitaxel backbone or not. Carboplatin was administered in an AUC of 5, the paclitaxel was administered at 175 mg/m2, and the bevacizumab was given at 15 mg/kg.

They found that there was an improvement in overall survival that was approximately 42.6 versus 37.3 months in terms of the medians. The hazard ratio was 0.84 or 0.82, depending on how it was calculated. That achieved barely statistical significance when you did the one based off the electronic case report forms. So, this was a very important study because we actually now have an improvement of almost 5 months in overall survival, which is very welcomed. The other thing that’s really important to point out is that you had a higher response rate as well, about 78% versus 57%.

The second phase III trial was an older trial, but it looked at carboplatin and gemcitabine. Carboplatin was given in an AUC of 4, the gemcitabine was given at 1000 mg/m2 combined with bevacizumab at the same dose as the GOG-213 trial. The OCEANS trial was with gemcitabine. And what we found was there an improvement in progression-free survival of about 4 months. Again, we saw the same increase in response rate—about 56% all the way up to 78% when you added the bevacizumab. So, very positive data.

If you look at the hazard ratio for the primary endpoint, it was 0.46—a very large benefit to receiving the bevacizumab in this case. Both of these trials are interesting because the bevacizumab was continued until disease progression or until toxicity. So, I think in terms of, how do you administer the bevacizumab? The advice would be to continue therapy until either of those 2 endpoints occurs.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Best Practice™: Expert Perspectives to Incorporate Evidence on PARP Inhibitors into Practice and Optimize the Medical Management of Ovarian CancerOct 31, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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