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Sequencing Therapies in Advanced Lung Adenocarcinoma

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: Thursday, Dec 22, 2016


Transcript:

Joachim G. Aerts, MD, PhD:
With all these new options coming up, we have now to decide how to sequence all our treatments. And, this is difficult. But, on the other hand, we also have to keep in mind that, in general, these patients are rapid progressors and have a short lifetime, and also have a rapid decrease in their performance status. You cannot just decide do first-line treatment, then do immunotherapy, and then see what I can give next, because you will lose a lot of patients who, after they failed efforts to introduce immunotherapy, will not be able to get chemotherapy as a further line. So, we really have to decide after the first line which is the treatment I want to give to this patient already, and that can be based on things like rapid progressor, PD-L1 positivity, and patient’s own preference, which we also have to take into account.

Marina Garassino, MD: There are also several data suggesting that we can use anti-angiogenics in first line and also in second line. In fact, if you look at the subgroup analysis of the REVEL trial, you can see that about 15% of patients were already treated with bevacizumab in first line. So, in principle, we can use these kinds of drugs everywhere in the treatment of these kinds of patients. However, I think that the best place to use the ramucirumab will be the second line. I think that the story is quite closed for squamous cell carcinoma because the advantage of immunotherapy in this setting is very high. I think that we have to talk again about use in the adenocarcinoma patients. And, for adenocarcinoma, I think that you have to look at the PD-L1 expression and then decide what to do. But, I think that skipping the combination therapy with docetaxel and anti-angiogenics could leave out a treatment option for a patient.

So, I think that although PD-L1 expression is not a good predictive biomarker, this is something that we must look at to decide all the treatment strategies from the first line to the end of the treatment of these kinds of patients. And we must try, with all this information, to give all the opportunities for these patients and to give all the treatment that is possible in their lives.

There is another point that must be very carefully considered, and this is the possibility of pembrolizumab as the first-line treatment for patients, strong expressers of PD-L1. So, all the patients who were strong expressers for PD-L1 and were treated with immunotherapy in first line, I’m sure that they will receive chemotherapy plus anti-angiogenics as second line if the performance status will permit this.

Roy S. Herbst, MD, PhD: Sequencing would be to save ramucirumab for the second, or more, line, and I would use ramucirumab in combination with docetaxel in the second, or more, line of therapy. Again, when you would use immunotherapy is a variable there. Most of the time, now, people are using immunotherapy second line, so it usually becomes a third-line combination.

Transcript Edited for Clarity
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Transcript:

Joachim G. Aerts, MD, PhD:
With all these new options coming up, we have now to decide how to sequence all our treatments. And, this is difficult. But, on the other hand, we also have to keep in mind that, in general, these patients are rapid progressors and have a short lifetime, and also have a rapid decrease in their performance status. You cannot just decide do first-line treatment, then do immunotherapy, and then see what I can give next, because you will lose a lot of patients who, after they failed efforts to introduce immunotherapy, will not be able to get chemotherapy as a further line. So, we really have to decide after the first line which is the treatment I want to give to this patient already, and that can be based on things like rapid progressor, PD-L1 positivity, and patient’s own preference, which we also have to take into account.

Marina Garassino, MD: There are also several data suggesting that we can use anti-angiogenics in first line and also in second line. In fact, if you look at the subgroup analysis of the REVEL trial, you can see that about 15% of patients were already treated with bevacizumab in first line. So, in principle, we can use these kinds of drugs everywhere in the treatment of these kinds of patients. However, I think that the best place to use the ramucirumab will be the second line. I think that the story is quite closed for squamous cell carcinoma because the advantage of immunotherapy in this setting is very high. I think that we have to talk again about use in the adenocarcinoma patients. And, for adenocarcinoma, I think that you have to look at the PD-L1 expression and then decide what to do. But, I think that skipping the combination therapy with docetaxel and anti-angiogenics could leave out a treatment option for a patient.

So, I think that although PD-L1 expression is not a good predictive biomarker, this is something that we must look at to decide all the treatment strategies from the first line to the end of the treatment of these kinds of patients. And we must try, with all this information, to give all the opportunities for these patients and to give all the treatment that is possible in their lives.

There is another point that must be very carefully considered, and this is the possibility of pembrolizumab as the first-line treatment for patients, strong expressers of PD-L1. So, all the patients who were strong expressers for PD-L1 and were treated with immunotherapy in first line, I’m sure that they will receive chemotherapy plus anti-angiogenics as second line if the performance status will permit this.

Roy S. Herbst, MD, PhD: Sequencing would be to save ramucirumab for the second, or more, line, and I would use ramucirumab in combination with docetaxel in the second, or more, line of therapy. Again, when you would use immunotherapy is a variable there. Most of the time, now, people are using immunotherapy second line, so it usually becomes a third-line combination.

Transcript Edited for Clarity
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