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Progression in Non-Driver Adenocarcinoma

Panelists:Benjamin P. Levy, MD, Mount Sinai Health Systems;Chandra P. Belani, MD, Penn State Cancer Institute;Marina Garassino, MD, National Cancer Institute Milan, Italy;Sarah B. Goldberg, MD, MPH, Yale Cancer Center;Ramaswamy Govindan, MD, Washington University School of Medicine;Mark G. Kris, MD, Memorial Sloan-Kettering Cancer Center
Published: Wednesday, Sep 14, 2016


Transcript:

Benjamin P. Levy, MD:
Patients that have identifiable mutations who are on targeted therapies develop resistance. The same story rings true for patients who are on chemotherapy. Maintenance is important for patients who are receiving chemotherapy. I think that maintenance discussion has to happen at the beginning of treatment, not when you’re ready to deliver maintenance. And we’ve seen improvements in PFS and OS with this strategy. But even with patients who receive maintenance, they will progress at some point. And outside of a clinical trial and outside of immunotherapy, maybe you could walk us through your treatment approach, given your work in the second-line space with docetaxel, and how you approach these patients.

Marina Garassino, MD: We have data on at least several drugs. We have data on docetaxel alone, on erlotinib, and on pemetrexed. We have data on the combination of docetaxel and nintedanib. We have data on the combination of docetaxel and ramucirumab. And now we have data on the combination of weekly paclitaxel and bevacizumab. We can say that antiangiogenics work, and we can endorse antiangiogenics in second-line—nintedanib and ramucirumab more or less. My feeling is that comparing the other ratios are more or less the same, so you can discuss with the patient if he prefers an oral treatment or intravenous treatment.

And also now there is the option of bevacizumab. The prospective of the European and Italian situation is that we have also to see the clinical relevance of the benefit. Because, also for the economical crisis, we have to know if we can have more benefit for all patients. And I think that chemotherapy will not die either in second-line—because immunotherapy will not be for all the patients—when we will understand, maybe in the next years, who are the patients really benefitting of immunotherapy.

Benjamin P. Levy, MD: So, if you’re not using an immunotherapy, and I would argue that immunotherapy is certainly cemented as a second-line treatment for those that are immunotherapy eligible, is your go-to regimen docetaxel? Is it docetaxel plus ramucirumab? We have, now, data coming out tomorrow looking at weekly paclitaxel with bevacizumab, showing an improvement in response rates versus docetaxel alone. Where do you sort this all out in your mind?

Marina Garassino, MD: If you have carboplatin/Taxol/bevacizumab in first-line, you may have also pemetrexed, which I think is more feasible than docetaxel. Otherwise, in my opinion, although the other ratio of paclitaxel plus bevacizumab seems higher and seems better than the other two combinations, more or less all the three options are the same.

Benjamin P. Levy, MD: Any other perspectives from the panel as how we approach second-line patients that aren’t getting immunotherapy, docetaxel/ramucirumab? We have a lot of competing strategies here. Mark, your thoughts?

Mark G. Kris, MD: I have no patients not getting immunotherapy.

Benjamin P. Levy, MD: Right. Maybe we should say this is a not eligible for immunotherapy second-line or third-line.

Mark G. Kris, MD: I pretty much agree with Marina, everything she said there. Just one thing I do want to bring up, though. I think giving an EGFR TKI in that setting is not something that can be highly recommended. They’re FDA-approved in a couple situations. However, in this targeted therapy milieu, and if you follow the ASCO guidelines there about choosing wisely, you don’t give targeted drugs to people without the target. And I urge people to back away from that, particularly our European friends who did it a lot. If you’re tempted to do it, that might be a place for that Biodesix test, the VeriStrat test. Because at least it would tell you it would keep some people from getting that drug. But I’d stay away from that. And we have so many other better choices now. I think that was Marina’s point.

Benjamin P. Levy, MD: Govindan, your approach to this?

Ramaswamy Govindan, MD: Same thing. I tend to use docetaxel as a conventional option. I’ve not used much of ramucirumab, but I think I agree with all the points made here.

Transcript Edited for Clarity
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Transcript:

Benjamin P. Levy, MD:
Patients that have identifiable mutations who are on targeted therapies develop resistance. The same story rings true for patients who are on chemotherapy. Maintenance is important for patients who are receiving chemotherapy. I think that maintenance discussion has to happen at the beginning of treatment, not when you’re ready to deliver maintenance. And we’ve seen improvements in PFS and OS with this strategy. But even with patients who receive maintenance, they will progress at some point. And outside of a clinical trial and outside of immunotherapy, maybe you could walk us through your treatment approach, given your work in the second-line space with docetaxel, and how you approach these patients.

Marina Garassino, MD: We have data on at least several drugs. We have data on docetaxel alone, on erlotinib, and on pemetrexed. We have data on the combination of docetaxel and nintedanib. We have data on the combination of docetaxel and ramucirumab. And now we have data on the combination of weekly paclitaxel and bevacizumab. We can say that antiangiogenics work, and we can endorse antiangiogenics in second-line—nintedanib and ramucirumab more or less. My feeling is that comparing the other ratios are more or less the same, so you can discuss with the patient if he prefers an oral treatment or intravenous treatment.

And also now there is the option of bevacizumab. The prospective of the European and Italian situation is that we have also to see the clinical relevance of the benefit. Because, also for the economical crisis, we have to know if we can have more benefit for all patients. And I think that chemotherapy will not die either in second-line—because immunotherapy will not be for all the patients—when we will understand, maybe in the next years, who are the patients really benefitting of immunotherapy.

Benjamin P. Levy, MD: So, if you’re not using an immunotherapy, and I would argue that immunotherapy is certainly cemented as a second-line treatment for those that are immunotherapy eligible, is your go-to regimen docetaxel? Is it docetaxel plus ramucirumab? We have, now, data coming out tomorrow looking at weekly paclitaxel with bevacizumab, showing an improvement in response rates versus docetaxel alone. Where do you sort this all out in your mind?

Marina Garassino, MD: If you have carboplatin/Taxol/bevacizumab in first-line, you may have also pemetrexed, which I think is more feasible than docetaxel. Otherwise, in my opinion, although the other ratio of paclitaxel plus bevacizumab seems higher and seems better than the other two combinations, more or less all the three options are the same.

Benjamin P. Levy, MD: Any other perspectives from the panel as how we approach second-line patients that aren’t getting immunotherapy, docetaxel/ramucirumab? We have a lot of competing strategies here. Mark, your thoughts?

Mark G. Kris, MD: I have no patients not getting immunotherapy.

Benjamin P. Levy, MD: Right. Maybe we should say this is a not eligible for immunotherapy second-line or third-line.

Mark G. Kris, MD: I pretty much agree with Marina, everything she said there. Just one thing I do want to bring up, though. I think giving an EGFR TKI in that setting is not something that can be highly recommended. They’re FDA-approved in a couple situations. However, in this targeted therapy milieu, and if you follow the ASCO guidelines there about choosing wisely, you don’t give targeted drugs to people without the target. And I urge people to back away from that, particularly our European friends who did it a lot. If you’re tempted to do it, that might be a place for that Biodesix test, the VeriStrat test. Because at least it would tell you it would keep some people from getting that drug. But I’d stay away from that. And we have so many other better choices now. I think that was Marina’s point.

Benjamin P. Levy, MD: Govindan, your approach to this?

Ramaswamy Govindan, MD: Same thing. I tend to use docetaxel as a conventional option. I’ve not used much of ramucirumab, but I think I agree with all the points made here.

Transcript Edited for Clarity
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