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Clinical Implications of the REVEL Trial in NSCLC

Insights From: Benjamin P. Levy, MD, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center; Ronald J. Scheff, MD, Weill Cornell Medical College; Ann Tsao, MD, MD Anderson Cancer Center
Published: Tuesday, May 01, 2018



Transcript: 

Ronald J. Scheff, MD: I think that when we’re talking about anti-VEGF therapy, it’s exciting because we have data for using bevacizumab in the frontline setting. In particular, in my practice, I use it with paclitaxel and carboplatin. And in the second-line setting, in the REVEL trial, we see that ramucirumab adds benefit to docetaxel. So, my patients, almost all of them at some point see anti-VEGF therapy.

Benjamin P. Levy, MD: From a biological standpoint, I’m not sure we know for these treatment-refractory patients why the addition of ramucirumab offered such a meaningful improvement in survival. Clearly, VEGF is at play. I think that’s probably my best guess, that these patients who are rapidly progressing, VEGF and VEGF elaboration is certainly driving the tumor to grow. And by offering these patients ramucirumab, you’re able to impact outcomes. So, I think there’s a lot to be explored scientifically there, but certainly clinically the observation is consistent for this group of patients.

Patients who are rapidly progressing on a platinum doublet, there needs to be a consideration for ramucirumab with docetaxel. Not that every patient is going to get that combination. Some are going to get immunotherapy, but the data are fairly convincing that this needs to be at least a consideration. I’ve had this in my practice where patients who have a low PD-L1 score, who are never-smokers, who are unlikely to respond to immunotherapy are rapidly progressing on a platinum doublet, perhaps platinum/pemetrexed with or without bevacizumab. And when they’re progressing, this is a patient where I would consider using docetaxel and ramucirumab, knowing that immunotherapy may not elicit responses in these patients.

For me, I generally start at a little bit lower dose with docetaxel. The recommended dose is 75 mg/m2. Sometimes I’ll go down to 60 mg/m2. I think the toxicity is manageable. I think we have to inform our patients what to expect. There’s a very low risk of bleeding with ramucirumab. There’s a very low risk of clotting. But we have to be careful with some cytopenias, specifically leucopenia and neutropenia. So, those are things that I look out for, but usually the toxicities are fairly manageable. For several of my patient cases, we are able to elicit responses and stabilize the tumor, which I think is meaningful for the patient.

Ann Tsao, MD: We oftentimes have patients in our practice where they rapidly progressed through our frontline treatments, even though they’re getting very aggressive therapy. And as I mentioned before, our field is rapidly progressing. So, we are changing the paradigm very frequently. But I have used docetaxel/ramucirumab in my patients who I’m very concerned that we don’t have that kind of time to see if an immunotherapy monotherapy will work, and if they don’t carry the biomarkers that are potentially predictive of a response. And I have had success with some of my patients who are rapidly progressing, progressed right through immunotherapy, for instance, and are pretty much in danger. And these are patients who still have a good performance status and can tolerate this treatment, and we’ve been able to get their disease back under control.

Ronald J. Scheff, MD: In my practice, I do incorporate anti-VEGF therapy at some point during the patient’s course, either in the first-line setting using bevacizumab in combination with paclitaxel and carboplatin or in the second-line setting with using ramucirumab with docetaxel. And, again, based on the REVEL trial for patients who receive bevacizumab up front, I do use ramucirumab in the second-line setting as well. Or, if I’m using immunotherapy in the second-line setting, I use ramucirumab and docetaxel in the third-line setting.

Transcript Edited for Clarity 
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Transcript: 

Ronald J. Scheff, MD: I think that when we’re talking about anti-VEGF therapy, it’s exciting because we have data for using bevacizumab in the frontline setting. In particular, in my practice, I use it with paclitaxel and carboplatin. And in the second-line setting, in the REVEL trial, we see that ramucirumab adds benefit to docetaxel. So, my patients, almost all of them at some point see anti-VEGF therapy.

Benjamin P. Levy, MD: From a biological standpoint, I’m not sure we know for these treatment-refractory patients why the addition of ramucirumab offered such a meaningful improvement in survival. Clearly, VEGF is at play. I think that’s probably my best guess, that these patients who are rapidly progressing, VEGF and VEGF elaboration is certainly driving the tumor to grow. And by offering these patients ramucirumab, you’re able to impact outcomes. So, I think there’s a lot to be explored scientifically there, but certainly clinically the observation is consistent for this group of patients.

Patients who are rapidly progressing on a platinum doublet, there needs to be a consideration for ramucirumab with docetaxel. Not that every patient is going to get that combination. Some are going to get immunotherapy, but the data are fairly convincing that this needs to be at least a consideration. I’ve had this in my practice where patients who have a low PD-L1 score, who are never-smokers, who are unlikely to respond to immunotherapy are rapidly progressing on a platinum doublet, perhaps platinum/pemetrexed with or without bevacizumab. And when they’re progressing, this is a patient where I would consider using docetaxel and ramucirumab, knowing that immunotherapy may not elicit responses in these patients.

For me, I generally start at a little bit lower dose with docetaxel. The recommended dose is 75 mg/m2. Sometimes I’ll go down to 60 mg/m2. I think the toxicity is manageable. I think we have to inform our patients what to expect. There’s a very low risk of bleeding with ramucirumab. There’s a very low risk of clotting. But we have to be careful with some cytopenias, specifically leucopenia and neutropenia. So, those are things that I look out for, but usually the toxicities are fairly manageable. For several of my patient cases, we are able to elicit responses and stabilize the tumor, which I think is meaningful for the patient.

Ann Tsao, MD: We oftentimes have patients in our practice where they rapidly progressed through our frontline treatments, even though they’re getting very aggressive therapy. And as I mentioned before, our field is rapidly progressing. So, we are changing the paradigm very frequently. But I have used docetaxel/ramucirumab in my patients who I’m very concerned that we don’t have that kind of time to see if an immunotherapy monotherapy will work, and if they don’t carry the biomarkers that are potentially predictive of a response. And I have had success with some of my patients who are rapidly progressing, progressed right through immunotherapy, for instance, and are pretty much in danger. And these are patients who still have a good performance status and can tolerate this treatment, and we’ve been able to get their disease back under control.

Ronald J. Scheff, MD: In my practice, I do incorporate anti-VEGF therapy at some point during the patient’s course, either in the first-line setting using bevacizumab in combination with paclitaxel and carboplatin or in the second-line setting with using ramucirumab with docetaxel. And, again, based on the REVEL trial for patients who receive bevacizumab up front, I do use ramucirumab in the second-line setting as well. Or, if I’m using immunotherapy in the second-line setting, I use ramucirumab and docetaxel in the third-line setting.

Transcript Edited for Clarity 
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