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Chemotherapy + Pembrolizumab: A New Standard of Care?

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: Thursday, Jul 19, 2018



Transcript: 

Hossein Borghaei, DO: I would call the results of KEYNOTE-189 practice-changing because they establish a new paradigm and a new standard of care for the majority of patients we see in the clinic. Again, these are patients who do not have a molecularly driven tumor, and previously we treated them with chemotherapy alone followed by immunotherapy. Because the study firmly establishes that adding pembrolizumab to chemotherapy is superior in terms of PFS response and overall survival, I think it makes it the standard of care for a majority of our patients.

The question is in the nuances of this study. For instance, in the patient population with a PD-L1 expression greater than 50%, it is not clear to me that adding chemotherapy to pembrolizumab buys us a lot more over pembrolizumab. We have those data from earlier trials that were conducted in that particular patient group. For me, if I have someone with at least 50% PD-L1 expression, pembrolizumab remains the standard of care without having to add chemotherapy. Patients who fall between 1% and 49% definitely have a lot of advantage from this combination. For patients with less than 1% PD-L1, even though the PFS benefit was not significantly better, I think the overall response rate and survival were better.

In a scenario where I’m faced with a patient who has significant burden of disease, a lot of symptoms from their lung cancer, I think it’s hard not to use a combination that gives me a higher response rate than chemotherapy alone because that is the patient population that needs a reduction in the amount of tumor and reduction in the symptoms and all of that. I think overall, it makes it a very usable combination for a majority of our patients.

Vassiliki Papadimitrakopoulou, MD: There was a sea change in our attitude toward use of chemotherapy with immunotherapy from the data that were published previously with KEYNOTE-021. KEYNOTE-189 demonstrated that the early benefit we saw was confirmed in this study. Therefore, it allows the use of this combination regimen in all settings. Of course, the use of this regimen in patients with low PD-L1 expression comes with some caveats. This is an area that still requires improvement. Therefore, using this regimen without hesitation in patients with expression that is higher than 50% and patients with expression between 1% and 49% should be the norm. For patients with low expression, there is still benefit, but I believe that this an area where research will be very active.

Corey J. Langer, MD: As far as I’m concerned, the results of KEYNOTE-189 are unprecedented and astounding. From my standpoint, they really do define a new standard of care, particularly for those patients with no PD-L1 expression or between 0% and 49% expression. It becomes a bit more controversial and problematic for those patients with 50% or higher expression. Again, this is the standard of care for nonsquamous non–small cell lung cancer in the absence of molecular aberrations. If you do the math eliminating squamous cell carcinoma; eliminating patients who have EGFR mutations or ALK translocations; and eliminating patients who really aren’t candidates for pemetrexed, which includes older adults with renal compromise, we’re probably talking about 50% of the advanced non–small cell lung cancer population. Still, it’s a significant percentage. In the 50% or higher group, we have equally relevant and almost as promising phase III data for pembrolizumab alone, single agent, versus standard chemotherapy. One has to wonder whether adding chemotherapy to pembrolizumab in that cohort really enhances long-term survival. I would have equipoise, personally, to enroll my patients on a prospective randomized phase III trial comparing pembrolizumab with the triplet.

Transcript Edited for Clarity
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Transcript: 

Hossein Borghaei, DO: I would call the results of KEYNOTE-189 practice-changing because they establish a new paradigm and a new standard of care for the majority of patients we see in the clinic. Again, these are patients who do not have a molecularly driven tumor, and previously we treated them with chemotherapy alone followed by immunotherapy. Because the study firmly establishes that adding pembrolizumab to chemotherapy is superior in terms of PFS response and overall survival, I think it makes it the standard of care for a majority of our patients.

The question is in the nuances of this study. For instance, in the patient population with a PD-L1 expression greater than 50%, it is not clear to me that adding chemotherapy to pembrolizumab buys us a lot more over pembrolizumab. We have those data from earlier trials that were conducted in that particular patient group. For me, if I have someone with at least 50% PD-L1 expression, pembrolizumab remains the standard of care without having to add chemotherapy. Patients who fall between 1% and 49% definitely have a lot of advantage from this combination. For patients with less than 1% PD-L1, even though the PFS benefit was not significantly better, I think the overall response rate and survival were better.

In a scenario where I’m faced with a patient who has significant burden of disease, a lot of symptoms from their lung cancer, I think it’s hard not to use a combination that gives me a higher response rate than chemotherapy alone because that is the patient population that needs a reduction in the amount of tumor and reduction in the symptoms and all of that. I think overall, it makes it a very usable combination for a majority of our patients.

Vassiliki Papadimitrakopoulou, MD: There was a sea change in our attitude toward use of chemotherapy with immunotherapy from the data that were published previously with KEYNOTE-021. KEYNOTE-189 demonstrated that the early benefit we saw was confirmed in this study. Therefore, it allows the use of this combination regimen in all settings. Of course, the use of this regimen in patients with low PD-L1 expression comes with some caveats. This is an area that still requires improvement. Therefore, using this regimen without hesitation in patients with expression that is higher than 50% and patients with expression between 1% and 49% should be the norm. For patients with low expression, there is still benefit, but I believe that this an area where research will be very active.

Corey J. Langer, MD: As far as I’m concerned, the results of KEYNOTE-189 are unprecedented and astounding. From my standpoint, they really do define a new standard of care, particularly for those patients with no PD-L1 expression or between 0% and 49% expression. It becomes a bit more controversial and problematic for those patients with 50% or higher expression. Again, this is the standard of care for nonsquamous non–small cell lung cancer in the absence of molecular aberrations. If you do the math eliminating squamous cell carcinoma; eliminating patients who have EGFR mutations or ALK translocations; and eliminating patients who really aren’t candidates for pemetrexed, which includes older adults with renal compromise, we’re probably talking about 50% of the advanced non–small cell lung cancer population. Still, it’s a significant percentage. In the 50% or higher group, we have equally relevant and almost as promising phase III data for pembrolizumab alone, single agent, versus standard chemotherapy. One has to wonder whether adding chemotherapy to pembrolizumab in that cohort really enhances long-term survival. I would have equipoise, personally, to enroll my patients on a prospective randomized phase III trial comparing pembrolizumab with the triplet.

Transcript Edited for Clarity
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