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Combining Therapies with Antiangiogenic Antibodies

Insights From: Mark A. Socinski, MD, UPMC
Published: Friday, Mar 18, 2016


Transcript:

At this point, I think, given the data we’ve seen with bevacizumab as well as ramucirumab, targeting angiogenesis is an important strategy in the treatment of advanced non-small cell lung cancer. Currently, bevacizumab is indicated in the first-line setting in combination with carboplatin and paclitaxel, although many of us use it with carboplatin and pemetrexed based on the results of the PointBreak trial which showed those two regimens to be equivalent with regard to overall survival. And in December of 2014, we had the approval of ramucirumab in the second-line setting.

So now we have these two sequential options. Ramucirumab has been explored in the first-line setting in combination with standard doublets, and there was a signal there like we initially saw with bevacizumab. It’s hard to know the strength of that signal without a head-to-head comparison to bevacizumab, which it has not been studied to date. So we don’t know the relative efficacy of those two antibodies. What we do know is that we have the ability to use them sequentially in first- and second-line.

Incidentally, one point about the REVEL trial was that the investigators did allow patients to have received bevacizumab in the first-line setting. If I remember correctly, somewhere between 10% and 15% of patients had received bevacizumab first-line. In an analysis, these were small numbers, of course; the use of bevacizumab in the first line did not appear to alter the impact of ramucirumab in the second-line setting, and so I would not exclude patients treated first-line with bevacizumab for the use of ramucirumab in the second-line setting.

Inhibition of angiogenesis has been a proven strategy, and we’ve talked a lot about the data with bevacizumab as well as ramucirumab. The ability to use anti-angiogenic therapy through multiple lines of therapy is an advance. The majority of our patients do not have oncogenic drivers, so they do not necessarily fit in to the EGFR mutation space or ALK translocation space. The majority of our patients are being treated with chemotherapy. T

he two antibodies that we have, bevacizumab and ramucirumab, have been shown to provide additional benefit when added to standard chemotherapy. There are a few very provocative settings. I mentioned the data with EGFR mutation–positive non-small cell lung cancer, and the addition of bevacizumab in that population looks very provocative. I actually think we need more data before we decide if this is going to be a new standard of care in this population.

The mechanism of action for inhibiting angiogenesis is reducing vascular pressure within tumors, normalizing the vasculature, and that sort of thing, allowing perhaps immune cells to better penetrate the cancer. That may be an advantage for use of anti-angiogenic agents in combination with several of the new immunotherapeutic agents which we’re all excited about. So I think angiogenesis, again, has been a proven strategy. We have a couple of options for our patients through multiple lines of therapy, and I think there are a few areas of particular interest: the EGFR mutation–positive space, as well as the optimal way to combine antiangiogenic agents with the new immunotherapeutic agents.
                                                                                                                                                                                                                                                                                                               
Transcript Edited for Clarity
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Transcript:

At this point, I think, given the data we’ve seen with bevacizumab as well as ramucirumab, targeting angiogenesis is an important strategy in the treatment of advanced non-small cell lung cancer. Currently, bevacizumab is indicated in the first-line setting in combination with carboplatin and paclitaxel, although many of us use it with carboplatin and pemetrexed based on the results of the PointBreak trial which showed those two regimens to be equivalent with regard to overall survival. And in December of 2014, we had the approval of ramucirumab in the second-line setting.

So now we have these two sequential options. Ramucirumab has been explored in the first-line setting in combination with standard doublets, and there was a signal there like we initially saw with bevacizumab. It’s hard to know the strength of that signal without a head-to-head comparison to bevacizumab, which it has not been studied to date. So we don’t know the relative efficacy of those two antibodies. What we do know is that we have the ability to use them sequentially in first- and second-line.

Incidentally, one point about the REVEL trial was that the investigators did allow patients to have received bevacizumab in the first-line setting. If I remember correctly, somewhere between 10% and 15% of patients had received bevacizumab first-line. In an analysis, these were small numbers, of course; the use of bevacizumab in the first line did not appear to alter the impact of ramucirumab in the second-line setting, and so I would not exclude patients treated first-line with bevacizumab for the use of ramucirumab in the second-line setting.

Inhibition of angiogenesis has been a proven strategy, and we’ve talked a lot about the data with bevacizumab as well as ramucirumab. The ability to use anti-angiogenic therapy through multiple lines of therapy is an advance. The majority of our patients do not have oncogenic drivers, so they do not necessarily fit in to the EGFR mutation space or ALK translocation space. The majority of our patients are being treated with chemotherapy. T

he two antibodies that we have, bevacizumab and ramucirumab, have been shown to provide additional benefit when added to standard chemotherapy. There are a few very provocative settings. I mentioned the data with EGFR mutation–positive non-small cell lung cancer, and the addition of bevacizumab in that population looks very provocative. I actually think we need more data before we decide if this is going to be a new standard of care in this population.

The mechanism of action for inhibiting angiogenesis is reducing vascular pressure within tumors, normalizing the vasculature, and that sort of thing, allowing perhaps immune cells to better penetrate the cancer. That may be an advantage for use of anti-angiogenic agents in combination with several of the new immunotherapeutic agents which we’re all excited about. So I think angiogenesis, again, has been a proven strategy. We have a couple of options for our patients through multiple lines of therapy, and I think there are a few areas of particular interest: the EGFR mutation–positive space, as well as the optimal way to combine antiangiogenic agents with the new immunotherapeutic agents.
                                                                                                                                                                                                                                                                                                               
Transcript Edited for Clarity
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