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Frontline Therapeutic Decisions for Nondriver mNSCLC

Insights From: Hossein Borghaei, DO, Fox Chase Cancer Center; Corey J. Langer, MD, Perelman School of Medicine; Vassiliki Papadimitrakopoulou, MD, MD Anderson Cancer Center
Published: Wednesday, Jul 25, 2018



Transcript: 

Vassiliki Papadimitrakopoulou, MD: The use of immunotherapy in the frontline setting is of great benefit to the patients. However, in second-line therapy, there are no new emerging information that will have agents be active above and beyond chemotherapy. Therefore, for the majority of our patients, standard chemotherapy will remain the second-line treatment.

Corey J. Langer, MD: The results of KEYNOTE-189 do not necessarily apply to the entire patient population. We have to remember that individuals with poor performance status, PS2 or PS3, were not candidates for this clinical trial. Those with baseline immune-mediated diseases or autoimmune diseases once more were not candidates. That won’t necessarily prevent us from trying out this regimen in selected patients with mild autoimmune disease. Certainly, if someone has Graves thyroid disease, we can easily treat that individual. On the other hand, for an individual with significant rheumatoid arthritis or systemic lupus, I would have major pause in considering this sort of regimen. I would go with chemotherapy alone or potentially consider a chemotherapeutic combination with an angiogenesis inhibitor like bevacizumab.

Hossein Borghaei, DO: For patients who come in with a PD-L1 expression over 50%, I think my first inclination is to offer them pembrolizumab alone. I don’t think we have the data to suggest that in that particular patient population, chemotherapy is adding a lot more to pembrolizumab. We don’t want to do cross-trial comparisons, and that’s not what I’m going to do. But just looking at the numbers in terms of 1-year survival, it doesn’t seem that adding chemotherapy—at least based on KEYNOTE-189—added a whole lot more to it. Now, that being said, if I see somebody with a PD-L1 expression of 50% who is losing 2 pounds a week and has night sweats and fevers and is completely symptomatic, and I want something that would cause the tumor to shrink a little bit more, I think that’s where I would go to the chemotherapy combination in that particular setting. I don’t think there is this one-size-fit-all type of a strategy, and I think you have to decide based on the symptoms of the patient that is sitting across from you as to what they can or cannot tolerate. I think that’s how I would use the triple combination in this specific patient population with over 50% PD-L1 expression.

Vassiliki Papadimitrakopoulou, MD: How we choose therapy in the frontline setting when patients have tumors that express more than 50% PD-L1 is a dilemma in our practice. My choices are usually based on disease burden and fitness. For patients who have high disease burden and are very symptomatic, the absolute use of chemotherapy is likely beneficial. For patients who have lesser performance status or comorbid disease, the choice is easier for immunotherapy only.

Transcript Edited for Clarity 
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Transcript: 

Vassiliki Papadimitrakopoulou, MD: The use of immunotherapy in the frontline setting is of great benefit to the patients. However, in second-line therapy, there are no new emerging information that will have agents be active above and beyond chemotherapy. Therefore, for the majority of our patients, standard chemotherapy will remain the second-line treatment.

Corey J. Langer, MD: The results of KEYNOTE-189 do not necessarily apply to the entire patient population. We have to remember that individuals with poor performance status, PS2 or PS3, were not candidates for this clinical trial. Those with baseline immune-mediated diseases or autoimmune diseases once more were not candidates. That won’t necessarily prevent us from trying out this regimen in selected patients with mild autoimmune disease. Certainly, if someone has Graves thyroid disease, we can easily treat that individual. On the other hand, for an individual with significant rheumatoid arthritis or systemic lupus, I would have major pause in considering this sort of regimen. I would go with chemotherapy alone or potentially consider a chemotherapeutic combination with an angiogenesis inhibitor like bevacizumab.

Hossein Borghaei, DO: For patients who come in with a PD-L1 expression over 50%, I think my first inclination is to offer them pembrolizumab alone. I don’t think we have the data to suggest that in that particular patient population, chemotherapy is adding a lot more to pembrolizumab. We don’t want to do cross-trial comparisons, and that’s not what I’m going to do. But just looking at the numbers in terms of 1-year survival, it doesn’t seem that adding chemotherapy—at least based on KEYNOTE-189—added a whole lot more to it. Now, that being said, if I see somebody with a PD-L1 expression of 50% who is losing 2 pounds a week and has night sweats and fevers and is completely symptomatic, and I want something that would cause the tumor to shrink a little bit more, I think that’s where I would go to the chemotherapy combination in that particular setting. I don’t think there is this one-size-fit-all type of a strategy, and I think you have to decide based on the symptoms of the patient that is sitting across from you as to what they can or cannot tolerate. I think that’s how I would use the triple combination in this specific patient population with over 50% PD-L1 expression.

Vassiliki Papadimitrakopoulou, MD: How we choose therapy in the frontline setting when patients have tumors that express more than 50% PD-L1 is a dilemma in our practice. My choices are usually based on disease burden and fitness. For patients who have high disease burden and are very symptomatic, the absolute use of chemotherapy is likely beneficial. For patients who have lesser performance status or comorbid disease, the choice is easier for immunotherapy only.

Transcript Edited for Clarity 
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