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Antiangiogenic Antibodies vs TKIs in NSCLC

Insights From: Joachim G. Aerts, MD, PhD, Erasmus Medical Center Cancer Institute; Enriqueta Felip, MD, PhD, Vall d’Hebron University Hospital; Marina Garassino, MD, National Cancer Institute of Milan; Roy Herbst, MD, Yale School of Medicine
Published: Friday, Dec 30, 2016


Transcript:

Marina Garassino, MD:
Using monoclonal antibodies and using tyrosine kinase inhibitors has several differences. In one case, you clearly target one point, so you are targeting one receptor. In the other case, you are targeting multiple points, and this is the reason why the tyrosine kinase inhibitors have a broad spectrum of action. And they target multiple kinases, not only VEGF. This is also the reason why they have a different toxicity profile from targeting only VEGFR2. So, in one case, we have oral drugs with a different toxicity profile. Diarrhea can be something that is different between the 2 drugs, but they are oral. They also pay to be oral because they have variable pharmacokinetics from the monoclonal antibodies. So, for targeting in all the cases angiogenesis, we have a different type of targeting of angiogenesis.

If we look to the results of the REVEL study and the results of the LUME-Lung study, we can see that more or less the hazard ratio is similar in the end, at least for adenocarcinoma. But, in the case of REVEL, we can target all histologies. In the case of the LUME-Lung, we can use the drug only in adenocarcinoma. Then, there are some other differences in the studies. The main difference is that the LUME-Lung study has the progression-free survival objective and the REVEL study has overall survival. But, in the end, they gave similar results.

I think that we have to discuss with the patient that we have different toxicity profiles. In one case, we have the possibility to give an oral drug and the other possibility is we can give an intravenous drug. I think that, for example, again, if the patient is taking several pills for the disease, it’s quite difficult to give another oral drug, both for the compliance, but also for the pharmacokinetics of the drug. In my opinion, we will decide case-by-case with the patient what is the best for each patient.

Roy Herbst MD, PhD: In the United States case, there are no TKIs that we would use against VEGF in lung cancer. But, in general, when I’m thinking between a monoclonal antibody and TKI, a monoclonal antibody is IV and a TKI is normally oral. So, of course, it’s a little easier to give a TKI, all else being equal. However, a monoclonal antibody is much more specific. It’s monoclonal, so it’s against 1 target, whereas a tyrosine kinase inhibitor can have many effects on many different kinases—depending on the dose that you use, that’s why you’re getting the toxicities—the skin, the GI, and other side effects, like general fatigue. If you have a monoclonal antibody, it’s specific, and it works, of course you’d want to use that. It would have fewer pharmacokinetic interactions, too, by the way.

Transcript Edited for Clarity
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Transcript:

Marina Garassino, MD:
Using monoclonal antibodies and using tyrosine kinase inhibitors has several differences. In one case, you clearly target one point, so you are targeting one receptor. In the other case, you are targeting multiple points, and this is the reason why the tyrosine kinase inhibitors have a broad spectrum of action. And they target multiple kinases, not only VEGF. This is also the reason why they have a different toxicity profile from targeting only VEGFR2. So, in one case, we have oral drugs with a different toxicity profile. Diarrhea can be something that is different between the 2 drugs, but they are oral. They also pay to be oral because they have variable pharmacokinetics from the monoclonal antibodies. So, for targeting in all the cases angiogenesis, we have a different type of targeting of angiogenesis.

If we look to the results of the REVEL study and the results of the LUME-Lung study, we can see that more or less the hazard ratio is similar in the end, at least for adenocarcinoma. But, in the case of REVEL, we can target all histologies. In the case of the LUME-Lung, we can use the drug only in adenocarcinoma. Then, there are some other differences in the studies. The main difference is that the LUME-Lung study has the progression-free survival objective and the REVEL study has overall survival. But, in the end, they gave similar results.

I think that we have to discuss with the patient that we have different toxicity profiles. In one case, we have the possibility to give an oral drug and the other possibility is we can give an intravenous drug. I think that, for example, again, if the patient is taking several pills for the disease, it’s quite difficult to give another oral drug, both for the compliance, but also for the pharmacokinetics of the drug. In my opinion, we will decide case-by-case with the patient what is the best for each patient.

Roy Herbst MD, PhD: In the United States case, there are no TKIs that we would use against VEGF in lung cancer. But, in general, when I’m thinking between a monoclonal antibody and TKI, a monoclonal antibody is IV and a TKI is normally oral. So, of course, it’s a little easier to give a TKI, all else being equal. However, a monoclonal antibody is much more specific. It’s monoclonal, so it’s against 1 target, whereas a tyrosine kinase inhibitor can have many effects on many different kinases—depending on the dose that you use, that’s why you’re getting the toxicities—the skin, the GI, and other side effects, like general fatigue. If you have a monoclonal antibody, it’s specific, and it works, of course you’d want to use that. It would have fewer pharmacokinetic interactions, too, by the way.

Transcript Edited for Clarity
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