Select Topic:
Browse by Series:

The KEYNOTE-042 and IMpower150 PD-L1 Treatments

Panelists: Mark A. Socinski, MD, Florida Hospital Cancer Institute; Maximilian Hochmair, MD, Otto Wagner Spital; Suresh Senan, MRCP, FRCR, PhD, VU University Medical Center; Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Thomas E. Stinchcombe, MD, Duke University Health System
Published: Wednesday, Nov 21, 2018



Transcript: 

Mark A. Socinski, MD:
We saw at ASCO [American Society of Clinical Oncology] this year, KEYNOTE-042, which had the same design but brought the PD-L1 [programmed death-ligand 1] criteria down to 1% or greater—very similar to the CheckMate-026 data. What are your thoughts about the KEYNOTE-042 trial?

Leora Horn, MD, MSc, FRCPC: I see it as a negative study: The overall survival was technically positive, but when you look at the breakdown, almost 50% of patients on that study were PD-L1 greater than 50%; their survival mirrored the KEYNOTE-024 study.
Mark A. Socinski, MD: It kind of validates 024.

Leora Horn, MD, MSc, FRCPC: Yes, but in the 1% to 49% patients, this is not a regiment we should be using. We also have the MYSTIC study. We haven’t seen the data, but a negative press release in that cohort with DURVA [durvalumab] and tremelimumab shows that, in the 1% of patients, there’s no role for single-agent immunotherapy.

Mark A. Socinski, MD: The 1% to 49%, which was an exploratory analysis, wasn’t a convincing benefit to use monotherapy in that population.

Leora Horn, MD, MSc, FRCPC: No, the PFS wasn’t better, and the OS definitely wasn’t better.

Mark A. Socinski, MD: Max, your thoughts?

Maximilian Hochmair, MD: It’s important to announce the KEYNOTE-024 regarding the second line: It was not preplanned that the patient received pembrolizumab [Keytruda] in the chemotherapy arm. There was no plan to cross over, and that influences the OS profoundly. For me, I’m of the same opinion as Dr. Horn.

Mark A. Socinski, MD: In the population, we can refer to the KEYNOTE-189 paradigm of chemotherapy with pembrolizumab. Is that your thinking?

Leora Horn, MD, MSc, FRCPC: Yes.

Mark A. Socinski, MD: Let me challenge you: There is a patient who, let’s say their PD-L1 is 30%. Is there a patient in that group for whom you would pursue monotherapy? Are there certain situations in which this is feasible?

Maximilian Hochmair, MD: I would go when the patient refuses complete chemotherapy. It’s an option you can offer perhaps, but you don’t feel safe in this situation.

Mark A. Socinski, MD: Tom?

Thomas E. Stinchcombe, MD: We do have some patients who aren’t chemotherapy candidates or, like Max said, refuse chemotherapy. You have to be candid with them that you might not be offering the optimal therapy in this situation.

Mark A. Socinski, MD: A cautionary note, because it may be tempting for oncologists to use monotherapy in these patients because it’s so well tolerated: Remember, if you weren’t eligible to get chemotherapy, you weren’t eligible for the trial. So you’re kind of extrapolating a little bit to a population that would have been excluded because they weren’t appropriate for platinum-based doublets. I believe triplet therapy is proper for this population.

Thomas E. Stinchcombe, MD: I think carboplatin with pembrolizumab is fairly well tolerated, too.

Mark A. Socinski, MD: Let me extend the argument a bit, because, in addition to the carboplatin/pemetrexed plus pembrolizumab, we also saw data including this group on the other FDA [US Food and Drug Administration] platform, which was carboplatin/paclitaxel [Taxol]/bevacizumab [Avastin] plus or minus atezolizumab. Any thoughts on the IMpower150?

Thomas E. Stinchcombe, MD: It’s a positive trial and has a significant overall survival benefit. I’m hesitant to do cross-trial comparisons because the control arms performed differently in the 2 trials.

Mark A. Socinski, MD: Remember for IMpower150, you had to be eligible to get bevacizumab, for which many patients are not. It’s a different cohort.

Thomas E. Stinchcombe, MD: It will be an option soon, I expect, once approved in the United States. My hesitancy is with the taxane and bevacizumab toxicity: Some patients may be reluctant to use it. The key subgroup, of course, was the mutation-positive patients, which previously hadn’t been studied and did show a benefit in that subgroup, which we’ve struggled with.

Leora Horn, MD, MSc, FRCPC: I agree with Tom. When carboplatin/pemetrexed came along, we stopped using carboplatin/Taxol/bevacizumab. It’s hard to imagine that now, because there’s a quadruplet regiment, which is also going to be more expensive, I’m going to start using that as opposed to carboplatin/pemetrexed with a checkpoint inhibitor
.
Mark A. Socinski, MD: I’ll take a slightly altered view of that: I do not think it’s more expensive. You have 2 expensive drugs in each regimen: the carboplatin/paclitaxel or generic.

Leora Horn, MD, MSc, FRCPC: Sure.

Mark A. Socinski, MD: I agree with you. We did adopt the carboplatin/pemetrexed approach, but I still think in selected patients, I don’t want to necessarily disregard bevacizumab as an option for these patients. We don’t have unlimited options for therapies, so this still does play a role; although I will admit the complication of a 4-drug regiment is a little cumbersome, and it’s tough to do. It’s not for every patient. And again, eligibility criteria for bevacizumab are narrow.

Maximilian Hochmair, MD: I would like to indicate that in the IMpower150, the strongest settings are patients with an EGFR mutation and ALK pretreatment—there’s no option for TKIs [tyrosine kinase inhibitors] anymore. We should firstly use TKIs and switch when there’s progression. This is the strongest of the studies we are using for this patient cohort. As a regiment, this is not the best tolerated in comparison to carboplatin/pemetrexed, but it’s strong and shows a nice OS. Those are the patients we are going to use for this regiment.


Transcript Edited for Clarity

SELECTED
LANGUAGE
Slider Left
Slider Right


Transcript: 

Mark A. Socinski, MD:
We saw at ASCO [American Society of Clinical Oncology] this year, KEYNOTE-042, which had the same design but brought the PD-L1 [programmed death-ligand 1] criteria down to 1% or greater—very similar to the CheckMate-026 data. What are your thoughts about the KEYNOTE-042 trial?

Leora Horn, MD, MSc, FRCPC: I see it as a negative study: The overall survival was technically positive, but when you look at the breakdown, almost 50% of patients on that study were PD-L1 greater than 50%; their survival mirrored the KEYNOTE-024 study.
Mark A. Socinski, MD: It kind of validates 024.

Leora Horn, MD, MSc, FRCPC: Yes, but in the 1% to 49% patients, this is not a regiment we should be using. We also have the MYSTIC study. We haven’t seen the data, but a negative press release in that cohort with DURVA [durvalumab] and tremelimumab shows that, in the 1% of patients, there’s no role for single-agent immunotherapy.

Mark A. Socinski, MD: The 1% to 49%, which was an exploratory analysis, wasn’t a convincing benefit to use monotherapy in that population.

Leora Horn, MD, MSc, FRCPC: No, the PFS wasn’t better, and the OS definitely wasn’t better.

Mark A. Socinski, MD: Max, your thoughts?

Maximilian Hochmair, MD: It’s important to announce the KEYNOTE-024 regarding the second line: It was not preplanned that the patient received pembrolizumab [Keytruda] in the chemotherapy arm. There was no plan to cross over, and that influences the OS profoundly. For me, I’m of the same opinion as Dr. Horn.

Mark A. Socinski, MD: In the population, we can refer to the KEYNOTE-189 paradigm of chemotherapy with pembrolizumab. Is that your thinking?

Leora Horn, MD, MSc, FRCPC: Yes.

Mark A. Socinski, MD: Let me challenge you: There is a patient who, let’s say their PD-L1 is 30%. Is there a patient in that group for whom you would pursue monotherapy? Are there certain situations in which this is feasible?

Maximilian Hochmair, MD: I would go when the patient refuses complete chemotherapy. It’s an option you can offer perhaps, but you don’t feel safe in this situation.

Mark A. Socinski, MD: Tom?

Thomas E. Stinchcombe, MD: We do have some patients who aren’t chemotherapy candidates or, like Max said, refuse chemotherapy. You have to be candid with them that you might not be offering the optimal therapy in this situation.

Mark A. Socinski, MD: A cautionary note, because it may be tempting for oncologists to use monotherapy in these patients because it’s so well tolerated: Remember, if you weren’t eligible to get chemotherapy, you weren’t eligible for the trial. So you’re kind of extrapolating a little bit to a population that would have been excluded because they weren’t appropriate for platinum-based doublets. I believe triplet therapy is proper for this population.

Thomas E. Stinchcombe, MD: I think carboplatin with pembrolizumab is fairly well tolerated, too.

Mark A. Socinski, MD: Let me extend the argument a bit, because, in addition to the carboplatin/pemetrexed plus pembrolizumab, we also saw data including this group on the other FDA [US Food and Drug Administration] platform, which was carboplatin/paclitaxel [Taxol]/bevacizumab [Avastin] plus or minus atezolizumab. Any thoughts on the IMpower150?

Thomas E. Stinchcombe, MD: It’s a positive trial and has a significant overall survival benefit. I’m hesitant to do cross-trial comparisons because the control arms performed differently in the 2 trials.

Mark A. Socinski, MD: Remember for IMpower150, you had to be eligible to get bevacizumab, for which many patients are not. It’s a different cohort.

Thomas E. Stinchcombe, MD: It will be an option soon, I expect, once approved in the United States. My hesitancy is with the taxane and bevacizumab toxicity: Some patients may be reluctant to use it. The key subgroup, of course, was the mutation-positive patients, which previously hadn’t been studied and did show a benefit in that subgroup, which we’ve struggled with.

Leora Horn, MD, MSc, FRCPC: I agree with Tom. When carboplatin/pemetrexed came along, we stopped using carboplatin/Taxol/bevacizumab. It’s hard to imagine that now, because there’s a quadruplet regiment, which is also going to be more expensive, I’m going to start using that as opposed to carboplatin/pemetrexed with a checkpoint inhibitor
.
Mark A. Socinski, MD: I’ll take a slightly altered view of that: I do not think it’s more expensive. You have 2 expensive drugs in each regimen: the carboplatin/paclitaxel or generic.

Leora Horn, MD, MSc, FRCPC: Sure.

Mark A. Socinski, MD: I agree with you. We did adopt the carboplatin/pemetrexed approach, but I still think in selected patients, I don’t want to necessarily disregard bevacizumab as an option for these patients. We don’t have unlimited options for therapies, so this still does play a role; although I will admit the complication of a 4-drug regiment is a little cumbersome, and it’s tough to do. It’s not for every patient. And again, eligibility criteria for bevacizumab are narrow.

Maximilian Hochmair, MD: I would like to indicate that in the IMpower150, the strongest settings are patients with an EGFR mutation and ALK pretreatment—there’s no option for TKIs [tyrosine kinase inhibitors] anymore. We should firstly use TKIs and switch when there’s progression. This is the strongest of the studies we are using for this patient cohort. As a regiment, this is not the best tolerated in comparison to carboplatin/pemetrexed, but it’s strong and shows a nice OS. Those are the patients we are going to use for this regiment.


Transcript Edited for Clarity
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Rapid Reviews in Oncology®: Practice-Changing Data in Acute Myeloid Leukemia: A Rapid Update From Atlanta OnlineDec 21, 20182.0
Community Practice Connections™: 2nd Annual European Congress on Hematology™: Focus on Lymphoid MalignanciesDec 30, 20182.0
Publication Bottom Border
Border Publication
x